{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:36:30Z","timestamp":1791765390652,"version":"4.3.4"},"reference-count":226,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["DFG KA724\/31-1"],"award-info":[{"award-number":["DFG KA724\/31-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["470145176"],"award-info":[{"award-number":["470145176"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cellular senescence (CSEN) is caused by a variety of factors that trigger complex molecular pathways. These include telomere shortening, oncogene activation and replicative stress, as well as DNA damage caused by genotoxic anticancer drugs and endogenous and exogenous genotoxins. Here, we review the induction of CSEN by exogenous genotoxic insults resulting from food and environmental exposures. The available data show that genotoxins\/carcinogens in tobacco smoke and smokeless tobacco, in the environment, in food, beverages and life-style products induce CNS. The exposures include N-nitroso compounds, polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, acrylamide, heavy metals, fine dust, mycotoxins, phytotoxins, and phycotoxins. Also, heme in red meat contributes to CSEN as it catalyzes the formation of genotoxic species in the colon. Induction of CSEN by external genotoxins\/carcinogens is bound on the DNA damage response pathway (DDR), which relies on activation of the ATM\/ATR-CHK2\/CHK1-p53-p21 axis and the p53-independent p16\/p14 axis, eliciting cyclin-dependent kinase inhibition and permanent cell cycle arrest. Other factors that can be involved are DREAM, MAPK, cGAS\/Sting, and NF-\u03baB. The accumulation of non-repaired DNA damage triggering CSEN following external genotoxic exposures may contribute significantly to the amelioration of senescent cells and organ failure with age in humans. Senescent cells drive, via the senescence-associated secretory phenotype (SASP), inflammation that is involved in many diseases, including cancer. Although most of the studies were performed with in vitro cell systems, the consequences of CSEN induction by genotoxic nutritional components and environmental exposures seem to be underestimated. Since CSEN correlates with aging, it is reasonable to conclude that exogenous genotoxic pollutants contribute significantly to the aging process through CSEN induction. In light of these findings, it is deduced that reducing genotoxin exposures and using \u201crejuvenation\u201d supplements (senotherapeutics) are reasonable strategies to counteract cellular senescence and the aging process.<\/jats:p>","DOI":"10.3390\/ijms27052389","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:11:36Z","timestamp":1772629896000},"page":"2389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cellular Senescence Triggered by Food and Environmental Genotoxins"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8217-0809","authenticated-orcid":false,"given":"Bernd","family":"Kaina","sequence":"first","affiliation":[{"name":"Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9289-4168","authenticated-orcid":false,"given":"Maja T.","family":"Tomicic","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9672-231X","authenticated-orcid":false,"given":"Markus","family":"Christmann","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.biopha.2007.10.006","article-title":"Lifestyle-related factors and environmental agents causing cancer: An overview","volume":"61","author":"Irigaray","year":"2007","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","first-page":"13","article-title":"DNA damage induced by endogenous aldehydes: Current state of knowledge","volume":"711","author":"Voulgaridou","year":"2011","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.freeradbiomed.2006.09.030","article-title":"Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function","volume":"42","author":"Fialkow","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/carcin\/18.4.811","article-title":"Wavelength dependence of oxidative DNA damage induced by UV and visible light","volume":"18","author":"Kielbassa","year":"1997","journal-title":"Carcinogenesis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.canlet.2012.04.005","article-title":"Oxidatively generated complex DNA damage: Tandem and clustered lesions","volume":"327","author":"Cadet","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.canlet.2012.01.007","article-title":"DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis","volume":"332","author":"Roos","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ponath, V., and Kaina, B. (2017). Death of Monocytes through Oxidative Burst of Macrophages and Neutrophils: Killing in Trans. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170347"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1124\/pharmrev.122.000622","article-title":"Cellular Senescence: From Mechanisms to Current Biomarkers and Senotherapies","volume":"75","author":"Lucas","year":"2023","journal-title":"Pharmacol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nrc2342","article-title":"DNA repair pathways as targets for cancer therapy","volume":"8","author":"Helleday","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.molmed.2007.07.001","article-title":"From traditional Chinese medicine to rational cancer therapy","volume":"13","author":"Efferth","year":"2007","journal-title":"Trends Mol. Med."},{"key":"ref_11","first-page":"797","article-title":"The eucalyptus oil ingredient 1,8-cineol induces oxidative DNA damage","volume":"89","author":"Wu","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1083\/jcb.201312078","article-title":"DNA breaks and chromosomal aberrations arise when replication meets base excision repair","volume":"206","author":"Ensminger","year":"2014","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kaina, B. (2023). Temozolomide, Procarbazine and Nitrosoureas in the Therapy of Malignant Gliomas: Update of Mechanisms, Drug Resistance and Therapeutic Implications. J. Clin. Med., 12.","DOI":"10.3390\/jcm12237442"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/sj.onc.1207080","article-title":"Apoptosis triggered by DNA damage O6-methylguanine in human lymphocytes requires DNA replication and is mediated by p53 and Fas\/CD95\/Apo-1","volume":"23","author":"Roos","year":"2004","journal-title":"Oncogene"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.mrrev.2008.09.001","article-title":"How DNA lesions are turned into powerful killing structures: Insights from UV-induced apoptosis","volume":"681","author":"Batista","year":"2009","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_16","first-page":"823","article-title":"Blockage of RNA polymerase as a possible trigger for u.v. light-induced apoptosis","volume":"13","author":"Ljungman","year":"1996","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.taap.2008.01.001","article-title":"Apoptotic death induced by the cyclophosphamide analogue mafosfamide in human lymphoblastoid cells: Contribution of DNA replication, transcription inhibition and Chk\/p53 signaling","volume":"229","author":"Goldstein","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1128\/MCB.21.1.281-288.2001","article-title":"DNA damage-dependent nuclear dynamics of the Mre11 complex","volume":"21","author":"Mirzoeva","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0092-8674(00)81175-7","article-title":"The hMre11\/hRad50 protein complex and Nijmegen breakage syndrome: Linkage of double-strand break repair to the cellular DNA damage response","volume":"93","author":"Carney","year":"1998","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature01368","article-title":"DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation","volume":"421","author":"Bakkenist","year":"2003","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13182","DOI":"10.1073\/pnas.0504211102","article-title":"A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM","volume":"102","author":"Sun","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrc1011","article-title":"ATM and related protein kinases: Safeguarding genome integrity","volume":"3","author":"Shiloh","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10389","DOI":"10.1073\/pnas.190030497","article-title":"Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro","volume":"97","author":"Matsuoka","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"42462","DOI":"10.1074\/jbc.C100466200","article-title":"ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks","volume":"276","author":"Burma","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1093\/nar\/gkr1300","article-title":"The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator","volume":"40","author":"Jungmichel","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1101\/gad.1301205","article-title":"Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint","volume":"19","author":"Byun","year":"2005","journal-title":"Genes Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1126\/science.1083430","article-title":"Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes","volume":"300","author":"Zou","year":"2003","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1091\/mbc.e04-11-1006","article-title":"ATRIP Binding to Replication Protein A-Single-stranded DNA Promotes ATR\u2013ATRIP Localization but Is Dispensable for Chk1 Phosphorylation","volume":"16","author":"Ball","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.dnarep.2004.03.032","article-title":"Dial 9-1-1 for DNA damage: The Rad9-Hus1-Rad1 (9-1-1) clamp complex","volume":"3","author":"Arlander","year":"2004","journal-title":"DNA Repair"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1101\/gad.1547007","article-title":"The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1","volume":"21","author":"Delacroix","year":"2007","journal-title":"Genes Dev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28036","DOI":"10.1074\/jbc.M704635200","article-title":"The Rad9-Hus1-Rad1 Checkpoint Clamp Regulates Interaction of TopBP1 with ATR","volume":"282","author":"Lee","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.cell.2005.12.041","article-title":"TopBP1 Activates the ATR-ATRIP Complex","volume":"124","author":"Kumagai","year":"2006","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1101\/gad.14.12.1448","article-title":"Chk1 is an essential kinase that is regulated by Atr and required for the G2\/M DNA damage checkpoint","volume":"14","author":"Liu","year":"2000","journal-title":"Genes Dev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"47759","DOI":"10.1074\/jbc.C100569200","article-title":"Histone H2AX Is Phosphorylated in an ATR-dependent Manner in Response to Replicational Stress","volume":"276","author":"Ward","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1101\/gad.851000","article-title":"Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress","volume":"14","author":"Tibbetts","year":"2000","journal-title":"Genes Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncb715","article-title":"Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2","volume":"4","author":"Hofmann","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrc.2015.2","article-title":"DNA damage and the balance between survival and death in cancer biology","volume":"16","author":"Roos","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0092-8674(95)90385-2","article-title":"The retinoblastoma protein and cell cycle control","volume":"81","author":"Weinberg","year":"1995","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1038\/sj.onc.1208612","article-title":"The E2F transcriptional network: Old acquaintances with new faces","volume":"24","author":"Dimova","year":"2005","journal-title":"Oncogene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/cdd.2017.172","article-title":"Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM","volume":"25","author":"Engeland","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.1093\/nar\/gkae426","article-title":"The p21CIP1-CDK4-DREAM axis is a master regulator of genotoxic stress-induced cellular senescence","volume":"52","author":"Schmidt","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41594-023-00942-8","article-title":"The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities","volume":"30","author":"Sendtner","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0092-8674(00)81400-2","article-title":"The Ink4a Tumor Suppressor Gene Product, p19Arf, Interacts with MDM2 and Neutralizes MDM2\u2019s Inhibition of p53","volume":"92","author":"Pomerantz","year":"1998","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0092-8674(00)81401-4","article-title":"ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways","volume":"92","author":"Zhang","year":"1998","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5001","DOI":"10.1093\/emboj\/17.17.5001","article-title":"The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2","volume":"17","author":"Stott","year":"1998","journal-title":"EMBO J."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tomicic, M.T., Kr\u00e4mer, F., Nguyen, A., Schwarzenbach, C., and Christmann, M. (2021). Oxaliplatin-Induced Senescence in Colorectal Cancer Cells Depends on p14ARF-Mediated Sustained p53 Activation. Cancers, 13.","DOI":"10.3390\/cancers13092019"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1128\/MCB.19.3.2109","article-title":"Differential Roles for Cyclin-Dependent Kinase Inhibitors p21 and p16 in the Mechanisms of Senescence and Differentiation in Human Fibroblasts","volume":"19","author":"Stein","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Safwan-Zaiter, H., Wagner, N., and Wagner, K.-D. (2022). P16INK4A\u2014More Than a Senescence Marker. Life, 12.","DOI":"10.3390\/life12091332"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1158\/1541-7786.MCR-08-0373","article-title":"p53 Deficiency Leads to Compensatory Up-Regulation of p16INK4a","volume":"7","author":"Leong","year":"2009","journal-title":"Mol. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117634","DOI":"10.1016\/j.biopha.2024.117634","article-title":"The cell cycle inhibitor p21CIP1 is essential for irinotecan-induced senescence and plays a decisive role in re-sensitization of temozolomide-resistant glioblastoma cells to irinotecan","volume":"181","author":"Sallbach","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/7050_014","article-title":"Induction of DNA repair genes in mammalian cells in response togenotoxic stress","volume":"Volume 1","author":"Lankenau","year":"2007","journal-title":"Genome Integrity: Facets and Perspectives"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Knizhnik, A.V., Roos, W.P., Nikolova, T., Quiros, S., Tomaszowski, K.-H., Christmann, M., and Kaina, B. (2013). Survival and Death Strategies in Glioma Cells: Autophagy, Senescence and Apoptosis Triggered by a Single Type of Temozolomide-Induced DNA Damage. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055665"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"He, Y., and Kaina, B. (2019). Are There Thresholds in Glioblastoma Cell Death Responses Triggered by Temozolomide?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071562"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","article-title":"Targeting NF-\u03baB pathway for the therapy of diseases: Mechanism and clinical study","volume":"5","author":"Yu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1600-065X.2012.01101.x","article-title":"DNA damage-dependent NF-\u03baB activation: NEMO turns nuclear signaling inside out","volume":"246","author":"McCool","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/cr.2010.179","article-title":"Nuclear initiated NF-\u03baB signaling: NEMO and ATM take center stage","volume":"21","author":"Miyamoto","year":"2010","journal-title":"Cell Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0092-8674(03)00895-X","article-title":"Sequential Modification of NEMO\/IKK\u03b3 by SUMO-1 and Ubiquitin Mediates NF-\u03baB Activation by Genotoxic Stress","volume":"115","author":"Huang","year":"2003","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1126\/science.1121513","article-title":"Molecular Linkage Between the Kinase ATM and NF-\u03baB Signaling in Response to Genotoxic Stimuli","volume":"311","author":"Wu","year":"2006","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.18632\/aging.102863","article-title":"ATM is a key driver of NF-\u03baB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging","volume":"12","author":"Zhao","year":"2020","journal-title":"Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41580-020-0244-x","article-title":"Molecular mechanisms and cellular functions of cGAS\u2013STING signalling","volume":"21","author":"Hopfner","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4451","DOI":"10.1074\/jbc.RA119.010734","article-title":"Autolysosomal degradation of cytosolic chromatin fragments antagonizes oxidative stress\u2013induced senescence","volume":"295","author":"Han","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"ra20","DOI":"10.1126\/scisignal.2002521","article-title":"STING Specifies IRF3 Phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway","volume":"5","author":"Tanaka","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1016\/j.molcel.2023.09.009","article-title":"TAK1 is an essential kinase for STING trafficking","volume":"83","author":"Ma","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1093\/nar\/gkw523","article-title":"Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks","volume":"44","author":"Fischer","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9087","DOI":"10.1093\/nar\/gkz635","article-title":"DREAM and RB cooperate to induce gene repression and cell-cycle arrest in response to p53 activation","volume":"47","author":"Uxa","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41419-018-0300-z","article-title":"Transcriptional repression of DNA repair genes is a hallmark and a cause of cellular senescence","volume":"9","author":"Collin","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"110752","DOI":"10.1016\/j.exger.2019.110752","article-title":"Regulation of senescence and the SASP by the transcription factor C\/EBP\u03b2","volume":"128","author":"Salotti","year":"2019","journal-title":"Exp. Gerontol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1101\/gad.17276711","article-title":"Control of the senescence-associated secretory phenotype by NF-\u03baB promotes senescence and enhances chemosensitivity","volume":"25","author":"Chien","year":"2011","journal-title":"Genes Dev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"21","DOI":"10.18632\/oncotarget.22940","article-title":"c-Myb and C\/EBP\u03b2 regulate OPN and other senescence-associated secretory phenotype factors","volume":"9","author":"Flanagan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/s41556-020-0529-5","article-title":"AP-1 imprints a reversible transcriptional programme of senescent cells","volume":"22","author":"Roux","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41514-024-00172-2","article-title":"The role of the dynamic epigenetic landscape in senescence: Orchestrating SASP expression","volume":"10","author":"Dasgupta","year":"2024","journal-title":"npj Aging"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.cell.2008.03.038","article-title":"Chemokine Signaling via the CXCR2 Receptor Reinforces Senescence","volume":"133","author":"Acosta","year":"2008","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1158\/0008-5472.CAN-05-1716","article-title":"The Gene Expression Program of Prostate Fibroblast Senescence Modulates Neoplastic Epithelial Cell Proliferation through Paracrine Mechanisms","volume":"66","author":"Bavik","year":"2006","journal-title":"Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s12307-011-0069-4","article-title":"Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts","volume":"5","author":"Laberge","year":"2011","journal-title":"Cancer Microenviron."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression","volume":"5","author":"Desprez","year":"2010","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1089\/ars.2020.8048","article-title":"Senescence in Post-Mitotic Cells: A Driver of Aging?","volume":"34","author":"Wan","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1474-9726.2010.00608.x","article-title":"Fat tissue, aging, and cellular senescence","volume":"9","author":"Tchkonia","year":"2010","journal-title":"Aging Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13578-022-00815-5","article-title":"The multifaceted role of the SASP in atherosclerosis: From mechanisms to therapeutic opportunities","volume":"12","author":"Sun","year":"2022","journal-title":"Cell Biosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s40035-024-00447-4","article-title":"Cellular senescence in Alzheimer\u2019s disease: From physiology to pathology","volume":"13","author":"Zhu","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"101652","DOI":"10.1016\/j.molmet.2022.101652","article-title":"p21 induces a senescence program and skeletal muscle dysfunction","volume":"67","author":"Englund","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Wyld, L., Bellantuono, I., Tchkonia, T., Morgan, J., Turner, O., Foss, F., George, J., Danson, S., and Kirkland, J.L. (2020). Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies. Cancers, 12.","DOI":"10.3390\/cancers12082134"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1164\/rccm.201810-1975TR","article-title":"Cellular Senescence as a Mechanism and Target in Chronic Lung Diseases","volume":"200","author":"Barnes","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/MNH.0000000000000782","article-title":"Ageing, cellular senescence and chronic kidney disease: Experimental evidence","volume":"31","author":"Tan","year":"2022","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Xu, J., Zhou, L., and Liu, Y. (2020). Cellular Senescence in Kidney Fibrosis: Pathologic Significance and Therapeutic Strategies. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.601325"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/ijmm.2025.5623","article-title":"Role of cellular senescence in hepatic diseases (Review)","volume":"56","author":"Xing","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.jid.2020.09.031","article-title":"Cellular Senescence and the Senescence-Associated Secretory Phenotype as Drivers of Skin Photoaging","volume":"141","author":"Fitsiou","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_87","first-page":"15","article-title":"The senescence-associated secretory phenotype and its regulation","volume":"117","author":"Rowell","year":"2018","journal-title":"Cytokine"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Beltzig, L., Schwarzenbach, C., Leukel, P., Frauenknecht, K.B.M., Sommer, C., Tancredi, A., Hegi, M.E., Christmann, M., and Kaina, B. (2022). Senescence Is the Main Trait Induced by Temozolomide in Glioblastoma Cells. Cancers, 14.","DOI":"10.3390\/cancers14092233"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/35085597","article-title":"TAK1 is a ubiquitin-dependent kinase of MKK and IKK","volume":"412","author":"Wang","year":"2001","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.freeradbiomed.2013.03.015","article-title":"Redox regulation of SIRT1 in inflammation and cellular senescence","volume":"61","author":"Hwang","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.yjmcc.2015.01.021","article-title":"Cellular and molecular biology of aging endothelial cells","volume":"89","author":"Donato","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Guan, G., Chen, Y., and Dong, Y. (2025). Unraveling the AMPK-SIRT1-FOXO Pathway: The In-Depth Analysis and Breakthrough Prospects of Oxidative Stress-Induced Diseases. Antioxidants, 14.","DOI":"10.3390\/antiox14010070"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zhao, K., Zhang, H., and Yang, D. (2024). SIRT1 exerts protective effects by inhibiting endoplasmic reticulum stress and NF-\u03baB signaling pathways. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1405546"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1101\/gad.1662308","article-title":"Akt-dependent regulation of NF-\u03baB is controlled by mTOR and Raptor in association with IKK","volume":"22","author":"Dan","year":"2008","journal-title":"Genes Dev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e12990","DOI":"10.1111\/acel.12990","article-title":"Forkhead box O3 protects the heart against paraquat-induced aging-associated phenotypes by upregulating the expression of antioxidant enzymes","volume":"18","author":"Chang","year":"2019","journal-title":"Aging Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0092-8674(04)00298-3","article-title":"Integration of Smad and Forkhead Pathways in the Control of Neuroepithelial and Glioblastoma Cell Proliferation","volume":"117","author":"Seoane","year":"2004","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1128\/MCB.26.1.28-38.2006","article-title":"Inhibition of SIRT1 Catalytic Activity Increases p53 Acetylation but Does Not Alter Cell Survival following DNA Damage","volume":"26","author":"Solomon","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1042\/BJ20080476","article-title":"Regulation of hypoxia-inducible factor-1alpha by NF-\u03baB","volume":"412","author":"Kenneth","year":"2008","journal-title":"Biochem. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"br3","DOI":"10.1091\/mbc.E24-10-0445","article-title":"The senescence-associated secretory phenotype constitutes HIF-1\u03b1 activation but is independent of micronuclei-induced cGAS\/STING activation","volume":"37","author":"Ho","year":"2026","journal-title":"Mol. Biol. Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jneuroim.2006.01.014","article-title":"Evidence that hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of interleukin-1\u03b2 (IL-1\u03b2) in astrocyte cultures","volume":"174","author":"Zhang","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e1447","DOI":"10.1002\/cti2.1447","article-title":"Hypoxia-inducible factor-1\u03b1 regulates the interleukin-6 production by B cells in rheumatoid arthritis","volume":"12","author":"Fan","year":"2023","journal-title":"Clin. Transl. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apcsb.2023.02.021","article-title":"Cellular senescence in aging: Molecular basis, implications and therapeutic interventions","volume":"136","author":"Princilly","year":"2023","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"030501","DOI":"10.11613\/BM.2019.030501","article-title":"Hallmarks of senescence and aging","volume":"29","author":"Dodig","year":"2019","journal-title":"Biochem. Medica"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12943-025-02284-z","article-title":"Regulation of cellular senescence in tumor progression and therapeutic targeting: Mechanisms and pathways","volume":"24","author":"Liu","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e13845","DOI":"10.1111\/acel.13845","article-title":"Cellular senescence in skin-related research: Targeted signaling pathways and naturally occurring therapeutic agents","volume":"22","author":"Stawny","year":"2023","journal-title":"Aging Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"101456","DOI":"10.1016\/j.arr.2021.101456","article-title":"How good is the evidence that cellular senescence causes skin ageing?","volume":"71","author":"Low","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Swiader, A., Camar\u00e9, C., Guerby, P., Salvayre, R., and Negre-Salvayre, A. (2021). 4-Hydroxynonenal Contributes to Fibroblast Senescence in Skin Photoaging Evoked by UV-A Radiation. Antioxidants, 10.","DOI":"10.3390\/antiox10030365"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1091\/mbc.e07-10-1041","article-title":"UVB-induced Senescence in Human Keratinocytes Requires a Functional Insulin-like Growth Factor-1 Receptor and p53","volume":"19","author":"Lewis","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Nyunoya, T., Monick, M., Lysek, G., Aykinburns, N., Klingelhutz, A., and Hunninghake, G. (2009, January 15\u201320). Cigarette Smoke Induces Cellular Senescence Via Werner\u2019s Syndrome Protein Downregulation. American Thoracic Society 2009 International Conference, San Diego, CA, USA.","DOI":"10.1164\/ajrccm-conference.2009.179.1_MeetingAbstracts.A1966"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1164\/rccm.200802-320OC","article-title":"Cigarette Smoke Induces Cellular Senescence via Werner\u2019s Syndrome Protein Down-regulation","volume":"179","author":"Nyunoya","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1165\/rcmb.2003-0290OC","article-title":"Cigarette Smoke Induces Senescence in Alveolar Epithelial Cells","volume":"31","author":"Tsuji","year":"2004","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6488","DOI":"10.1038\/s41598-020-63613-4","article-title":"Cigarette smoking induces human CCR6+Th17 lymphocytes senescence and VEGF-A secretion","volume":"10","author":"Baskara","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"106076","DOI":"10.1016\/j.tiv.2025.106076","article-title":"Cigarette sidestream smoke-induced cellular senescence and the protective role of histone H2AX","volume":"107","author":"Komaki","year":"2025","journal-title":"Toxicol. Vitro"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12931-014-0094-1","article-title":"Smoking accelerates aging of the small airway epithelium","volume":"15","author":"Walters","year":"2014","journal-title":"Respir. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.resinv.2021.09.003","article-title":"Cellular senescence\u2014An aging hallmark in chronic obstructive pulmonary disease pathogenesis","volume":"60","author":"Araya","year":"2022","journal-title":"Respir. Investig."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Aghali, A., Ngassie, M.L.K., Pabelick, C.M., and Prakash, Y.S. (2022). Cellular Senescence in Aging Lungs and Diseases. Cells, 11.","DOI":"10.3390\/cells11111781"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1164\/rccm.200509-1374OC","article-title":"Alveolar Cell Senescence in Patients with Pulmonary Emphysema","volume":"174","author":"Tsuji","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"14532","DOI":"10.1038\/ncomms14532","article-title":"Cellular senescence mediates fibrotic pulmonary disease","volume":"8","author":"Schafer","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1080\/10408444.2023.2264327","article-title":"From cultivation to cancer: Formation of N -nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications","volume":"53","author":"Stanfill","year":"2023","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"56","DOI":"10.4103\/ijmr.IJMR_2023_17","article-title":"Relationship between type of smokeless tobacco & risk of cancer: A systematic review","volume":"148","author":"Gupta","year":"2018","journal-title":"Indian J. Med. Res."},{"key":"ref_121","unstructured":"IARC (2010). Some non-heterocyclic polycyclic aromatic hydrocarbons and some related exposures. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_122","unstructured":"IARC (2012). Chemical agents and related occupations. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S1470-2045(09)70358-4","article-title":"A review of human carcinogens\u2014Part F: Chemical agents and related occupations","volume":"10","author":"Baan","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"139083","DOI":"10.1016\/j.jhazmat.2025.139083","article-title":"AhR-mediated histone lactylation drives cellular senescence during benzo[a]pyrene-evoked chronic obstructive pulmonary disease","volume":"495","author":"Chen","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1248\/bpb.b25-00309","article-title":"Effect of Benzo[a]pyrene on Cellular Senescence in MCF7 Breast Cancer Cells","volume":"48","author":"Kitamoto","year":"2025","journal-title":"Biol. Pharm. Bull."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"12085","DOI":"10.1093\/nar\/gkaa965","article-title":"Benzo[a]pyrene represses DNA repair through altered E2F1\/E2F4 function marking an early event in DNA damage-induced cellular senescence","volume":"48","author":"Allmann","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"116656","DOI":"10.1016\/j.taap.2023.116656","article-title":"TERT transcription and translocation into mitochondria regulate benzo[a]pyrene\/BPDE-induced senescence and mitochondrial damage in mouse spermatocytes","volume":"475","author":"Cui","year":"2023","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.envpol.2017.12.099","article-title":"TERT regulates telomere-related senescence and apoptosis through DNA damage response in male germ cells exposed to BPDE in vitro and to B[a]P in vivo","volume":"235","author":"Ling","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Fahrer, J., and Christmann, M. (2023). DNA Alkylation Damage by Nitrosamines and Relevant DNA Repair Pathways. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054684"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1021\/tx7002068","article-title":"Progress and Challenges in Selected Areas of Tobacco Carcinogenesis","volume":"21","author":"Hecht","year":"2007","journal-title":"Chem. Res. Toxicol."},{"key":"ref_131","unstructured":"IARC (2010). Personal Habits and Indoor Combustions. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_132","unstructured":"IARC (2007). Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/carcin\/7.3.393","article-title":"Formation and stability of alkylated pyrimidines and purines (including imidazole ring-opened 7-alkylguanine) and alkylphosphotriesters in liver DNA of adult rats treated with ethylnitrosourea or dimethylnitrosamine","volume":"7","author":"Engelse","year":"1986","journal-title":"Carcinogenesis"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Li, Y., and Hecht, S.S. (2022). Metabolism and DNA Adduct Formation of Tobacco-Specific N-Nitrosamines. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095109"},{"key":"ref_135","first-page":"127","article-title":"DNA adduct formation from tobacco-specific N-nitrosamines","volume":"424","author":"Hecht","year":"1999","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_136","first-page":"498","article-title":"Comparative tumorigenicity and dna methylation in f344 rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and n-nitrosodimethylamine","volume":"46","author":"Hecht","year":"1986","journal-title":"Cancer Res."},{"key":"ref_137","first-page":"64","article-title":"O6-methylguanine-DNA methyltransferase (MGMT): Impact on cancer risk in response to tobacco smoke","volume":"736","author":"Christmann","year":"2012","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/carcin\/12.2.257","article-title":"N-Nitroso compounds in cigarette tobacco and their occurrence in mainstream tobacco smoke","volume":"12","author":"Tricker","year":"1991","journal-title":"Carcinogenesis"},{"key":"ref_139","unstructured":"IARC (1987). Some N-Nitroso Compounds. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1053\/j.gastro.2009.11.008","article-title":"Induction of p53 Renders ATM-Deficient Mice Refractory to Hepatocarcinogenesis","volume":"138","author":"Teoh","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.toxlet.2015.11.011","article-title":"Double staining of \u03b2-galactosidase with fibrosis and cancer markers reveals the chronological appearance of senescence in liver carcinogenesis induced by diethylnitrosamine","volume":"241","author":"Shibayama","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.dnarep.2007.03.008","article-title":"MGMT: Key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents","volume":"6","author":"Kaina","year":"2007","journal-title":"DNA Repair"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1158\/0008-5472.CAN-18-1733","article-title":"Temozolomide Induces Senescence and Repression of DNA Repair Pathways in Glioblastoma Cells via Activation of ATR\u2013CHK1, p21, and NF-\u03baB","volume":"79","author":"Aasland","year":"2019","journal-title":"Cancer Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1007\/s11912-025-01733-8","article-title":"Senotherapeutics in Malignant Brain Cancer Therapy","volume":"27","author":"Kaina","year":"2025","journal-title":"Curr. Oncol. Rep."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1476-4598-3-3","article-title":"N-Methyl-N\u2019-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA","volume":"3","author":"Jaiswal","year":"2004","journal-title":"Mol. Cancer"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"102757","DOI":"10.1016\/j.redox.2023.102757","article-title":"A superoxide-driven redox state promotes geroconversion and resistance to senolysis in replication-stress associated senescence","volume":"64","author":"Luo","year":"2023","journal-title":"Redox Biol."},{"key":"ref_147","unstructured":"IARC (2012). Arsenic, Metals, Fibres, and Dusts. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/10408440500534032","article-title":"Toxicity and carcinogenicity of chromium compounds in humans","volume":"36","author":"Costa","year":"2006","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"A438","DOI":"10.1289\/ehp.99107a438","article-title":"Nickel carcinogenesis, mutation, epigenetics, or selection","volume":"107","author":"Costa","year":"1999","journal-title":"Environ. Health Perspect."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"tfae136","DOI":"10.1093\/toxres\/tfae136","article-title":"Research progress on the regulatory mechanism of cell senescence in arsenic toxicity: A systematic review","volume":"13","author":"Gu","year":"2024","journal-title":"Toxicol. Res."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Vielee, S.T., and Wise, J.P. (2023). Among Gerontogens, Heavy Metals Are a Class of Their Own: A Review of the Evidence for Cellular Senescence. Brain Sci., 13.","DOI":"10.3390\/brainsci13030500"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"118043","DOI":"10.1016\/j.envpol.2021.118043","article-title":"Cadmium exposure induces osteoporosis through cellular senescence, associated with activation of NF-\u03baB pathway and mitochondrial dysfunction","volume":"290","author":"Luo","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"114098","DOI":"10.1016\/j.ecoenv.2022.114098","article-title":"Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation","volume":"245","author":"Chou","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"110632","DOI":"10.1016\/j.cbi.2023.110632","article-title":"SIRT1 regulates osteoblast senescence through SOD2 acetylation and mitochondrial dysfunction in the progression of Osteoporosis caused by Cadmium exposure","volume":"382","author":"Zhou","year":"2023","journal-title":"Chem. Interact."},{"key":"ref_155","first-page":"588","article-title":"Cadmium-induced annulus fibrosus cell senescence contributes to intervertebral disc degeneration via the JNK\/p53 signaling pathway","volume":"27","author":"Liu","year":"2024","journal-title":"Iran J. Basic Med. Sci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"135103","DOI":"10.1016\/j.jhazmat.2024.135103","article-title":"Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury","volume":"476","author":"Peng","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"116231","DOI":"10.1016\/j.taap.2022.116231","article-title":"Inorganic arsenic exposure-induced premature senescence and senescence-associated secretory phenotype (SASP) in human hepatic stellate cells","volume":"454","author":"Okamura","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1265\/ehpm.24-00139","article-title":"Arsenite exposure induces premature senescence and senescence-associated secretory phenotype (SASP) in human hepatocyte-derived cell line Huh-7","volume":"29","author":"Okamura","year":"2024","journal-title":"Environ. Health Prev. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.taap.2017.05.029","article-title":"Nickel-induced HIF-1\u03b1 promotes growth arrest and senescence in normal human cells but lacks toxic effects in transformed cells","volume":"331","author":"Luczak","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"34578","DOI":"10.1038\/srep34578","article-title":"Cr(VI) induces premature senescence through ROS-mediated p53 pathway in L-02 hepatocytes","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"111908","DOI":"10.1016\/j.ecoenv.2021.111908","article-title":"Identification and functional analysis of senescence-associated secretory phenotype of premature senescent hepatocytes induced by hexavalent chromium","volume":"211","author":"Ma","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"113645","DOI":"10.1016\/j.ecoenv.2022.113645","article-title":"Hexavalent chromium triggers hepatocytes premature senescence via the GATA4\/NF-\u03baB signaling pathway mediated by the DNA damage response","volume":"239","author":"Ma","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"100490","DOI":"10.1016\/j.ocarto.2024.100490","article-title":"Cobalt ions induce a cellular senescence secretory phenotype in human synovial fibroblast-like cells that may be an early event in the development of adverse local tissue reactions to hip implants","volume":"6","author":"Grant","year":"2024","journal-title":"Osteoarthr. Cartil. Open"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1080\/17435390.2022.2147460","article-title":"Ambient PM2.5 exposure causes cellular senescence via DNA damage, micronuclei formation, and cGAS activation","volume":"16","author":"Wu","year":"2022","journal-title":"Nanotoxicology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0305-4","article-title":"Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications","volume":"51","author":"Ryu","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e2404142","DOI":"10.1002\/advs.202404142","article-title":"Chronic Exposure to Bioaerosols in PM2.5 from Garbage Stations Accelerates Vascular Aging via the NF-\u03baB\/NLRP3 Pathway","volume":"11","author":"Chen","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"307","DOI":"10.4049\/immunohorizons.2300096","article-title":"Air Pollution Drives Macrophage Senescence through a Phagolysosome\u201315-Lipoxygenase Pathway","volume":"8","author":"Yong","year":"2024","journal-title":"ImmunoHorizons"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"108489","DOI":"10.1016\/j.envint.2024.108489","article-title":"Microplastics exposure causes the senescence of human lung epithelial cells and mouse lungs by inducing ROS signaling","volume":"185","author":"Jin","year":"2024","journal-title":"Environ. Int."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Bulanda, S., and Janoszka, B. (2022). Consumption of Thermally Processed Meat Containing Carcinogenic Compounds (Polycyclic Aromatic Hydrocarbons and Heterocyclic Aromatic Amines) versus a Risk of Some Cancers in Humans and the Possibility of Reducing Their Formation by Natural Food Additives\u2014A Literature Review. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19084781"},{"key":"ref_170","unstructured":"IARC (1993). Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"10841","DOI":"10.1038\/s41598-017-11502-8","article-title":"In vitro exposure of simulated meat-cooking fumes to assess adverse biological effects","volume":"7","author":"Poudel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_172","unstructured":"IARC (1994). Some Industrial Chemicals. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1021\/tx500341z","article-title":"Acrylamide Induces Senescence in Macrophages through a Process Involving ATF3, ROS, p38\/JNK, and a Telomerase-Independent Pathway","volume":"28","author":"Kim","year":"2015","journal-title":"Chem. Res. Toxicol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.fct.2015.05.021","article-title":"Acrylamide induces accelerated endothelial aging in a human cell model","volume":"83","author":"Sellier","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"ref_175","first-page":"165","article-title":"Impact of Acrylamide on Cellular Senescence Response and Cell Cycle Distribution via an In-vitro Study","volume":"20","author":"Mahdizade","year":"2021","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1158\/1940-6207.CAPR-10-0113","article-title":"Heme iron from meat and risk of colorectal cancer: A meta-analysis and a review of the mechanisms involved","volume":"4","author":"Bastide","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"718","DOI":"10.2533\/chimia.2018.718","article-title":"Mechanistic Evidence for Red Meat and Processed Meat Intake and Cancer Risk: A Follow-up on the International Agency for Research on Cancer Evaluation of 2015","volume":"72","author":"Turesky","year":"2018","journal-title":"Chim. Int. J. Chem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"188334","DOI":"10.1016\/j.bbcan.2019.188334","article-title":"Mechanism of colorectal carcinogenesis triggered by heme iron from red meat","volume":"1873","author":"Seiwert","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA) - Rev. Cancer"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41419-020-02950-8","article-title":"Heme oxygenase 1 protects human colonocytes against ROS formation, oxidative DNA damage and cytotoxicity induced by heme iron, but not inorganic iron","volume":"11","author":"Seiwert","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1158\/0008-5472.CAN-14-2554","article-title":"A central role for heme iron in colon carcinogenesis associated with red meat intake","volume":"75","author":"Bastide","year":"2015","journal-title":"Cancer Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.critrevonc.2018.03.025","article-title":"The role of heme iron molecules derived from red and processed meat in the pathogenesis of colorectal carcinoma","volume":"126","author":"Gamage","year":"2018","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_182","first-page":"01","article-title":"The Peroxidation of Lipids, Cellular Senescence and Aging","volume":"12","author":"Monroe","year":"2024","journal-title":"J. Aging Sci."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/s42003-025-07983-3","article-title":"Hemin-induced transient senescence via DNA damage response: A neuroprotective mechanism against ferroptosis in intracerebral hemorrhage","volume":"8","author":"Malojirao","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1007\/s00204-021-03064-6","article-title":"Chronic intestinal inflammation drives colorectal tumor formation triggered by dietary heme iron in vivo","volume":"95","author":"Seiwert","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_185","unstructured":"IARC (2002). Some Naturally Occurring Substances: Food Items and Constituents, Herbs and Spices. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Huang, B., Chen, Q., Wang, L., Gao, X., Zhu, W., Mu, P., and Deng, Y. (2020). Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186517"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"9194","DOI":"10.1002\/jcp.27596","article-title":"Aflatoxin G1 induced TNF-\u03b1-dependent lung inflammation to enhance DNA damage in alveolar epithelial cells","volume":"234","author":"Shao","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_188","first-page":"385","article-title":"Roles of p21, p53, cyclin D1, CDK-4, estrogen receptor \u03b1 in aflatoxin B1-induced cytotoxicity in testicular tissue of mice","volume":"33","author":"Razi","year":"2017","journal-title":"Environ. Toxicol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1293\/tox.2018-0015","article-title":"Effects of aflatoxin B1 on the cell cycle distribution of splenocytes in chickens","volume":"32","author":"Li","year":"2019","journal-title":"J. Toxicol. Pathol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"110961","DOI":"10.1016\/j.intimp.2023.110961","article-title":"Aflatoxin B1 exposure triggers inflammation and premature skin aging via ERMCS\/Ca2+\/ROS signaling cascade","volume":"124","author":"Wu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.tox.2017.03.009","article-title":"Ochratoxin A induced premature senescence in human renal proximal tubular cells","volume":"382","author":"Yang","year":"2017","journal-title":"Toxicology"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"27864","DOI":"10.1007\/s11356-024-32696-1","article-title":"Ochratoxin A (OTA) causes intestinal aging damage through the NLRP3 signaling pathway mediated by calcium overload and oxidative stress","volume":"31","author":"Wang","year":"2024","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Dubourg, V., Nolze, A., Kopf, M., Gekle, M., and Schwerdt, G. (2020). Weighted Correlation Network Analysis Reveals CDK2 as a Regulator of a Ubiquitous Environmental Toxin-Induced Cell-Cycle Arrest. Cells, 9.","DOI":"10.3390\/cells9010143"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.toxlet.2020.05.011","article-title":"Effects of Ochratoxin A exposure on DNA damage in porcine granulosa cells in vitro","volume":"330","author":"Zhang","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1111\/jpn.13180","article-title":"Deoxynivalenol induces oxidative stress, inflammatory response and apoptosis in bovine mammary epithelial cells","volume":"103","author":"Wang","year":"2019","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/toxsci\/kfs106","article-title":"JAK\/STAT Pathway Plays a Critical Role in the Proinflammatory Gene Expression and Apoptosis of RAW264.7 Cells Induced by Trichothecenes as DON and T-2 Toxin","volume":"127","author":"Wang","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.tox.2007.10.002","article-title":"Ribotoxic mycotoxin deoxynivalenol induces G2\/M cell cycle arrest via p21Cip\/WAF1 mRNA stabilization in human epithelial cells","volume":"243","author":"Yang","year":"2008","journal-title":"Toxicology"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"153868","DOI":"10.1016\/j.tox.2024.153868","article-title":"Deoxynivalenol induces cell senescence in RAW264.7 macrophages via HIF-1\u03b1-mediated activation of the p53\/p21 pathway","volume":"506","author":"Li","year":"2024","journal-title":"Toxicology"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.tox.2014.10.009","article-title":"Autophagy and senescence, stress responses induced by the DNA-damaging mycotoxin alternariol","volume":"326","author":"Solhaug","year":"2014","journal-title":"Toxicology"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.toxlet.2015.08.1107","article-title":"The mycotoxin alternariol induces DNA damage and modify macrophage phenotype and inflammatory responses","volume":"239","author":"Solhaug","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"112326","DOI":"10.1016\/j.fct.2021.112326","article-title":"Fumonisin B1 induces poly (ADP-ribose) (PAR) polymer-mediated cell death (parthanatos) in neuroblastoma","volume":"154","author":"Paul","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.tox.2018.03.006","article-title":"The critical role of p16\/Rb pathway in the inhibition of GH3 cell cycle induced by T-2 toxin","volume":"400\u2013401","author":"Fatima","year":"2018","journal-title":"Toxicology"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"117464","DOI":"10.1016\/j.ecoenv.2024.117464","article-title":"T-2 toxin induces senescence in human neuroblastoma SH-SY5Y cells by regulating the HIF-1\u03b1\/p53\/p21 pathway","volume":"289","author":"Wang","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"24046","DOI":"10.1021\/acs.jafc.4c07268","article-title":"T-2 Toxin Induces Immunosenescence in RAW264.7 Macrophages by Activating the HIF-1\u03b1\/cGAS-STING Pathway","volume":"72","author":"Deng","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"56037","DOI":"10.1007\/s11356-023-25869-x","article-title":"Zearalenone induces the senescence of cardiovascular cells in vitro and in vivo","volume":"30","author":"Wang","year":"2023","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Han, X., Huangfu, B., Xu, T., Xu, W., Asakiya, C., Huang, K., and He, X. (2022). Research Progress of Safety of Zearalenone: A Review. Toxins, 14.","DOI":"10.3390\/toxins14060386"},{"key":"ref_207","unstructured":"IARC (1986). Some Naturally Occurring Substance. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_208","unstructured":"IARC (2004). Some Mycotoxins, and Other Naturally Occurring Substances. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_209","unstructured":"IARC (2012). A review of human carcinogens. IARC Monogr Eval Carcinog Risks to Humans, IARC."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Urate, S., Wakui, H., Azushima, K., Yamaji, T., Suzuki, T., Abe, E., Tanaka, S., Taguchi, S., Tsukamoto, S., and Kinguchi, S. (2021). Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212432"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1002\/hep.25698","article-title":"Hepatocyte senescence in vivo following preconditioning for liver repopulation","volume":"56","author":"Serra","year":"2012","journal-title":"Hepatology"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1007\/s00204-025-04185-y","article-title":"The pyrrolizidine alkaloid lasiocarpine impairs cell cycle progression in vitro","volume":"99","author":"Beckschulte","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/jop.12370","article-title":"Areca nut alkaloids induce irreparable DNA damage and senescence in fibroblasts and may create a favourable environment for tumour progression","volume":"45","author":"Rehman","year":"2015","journal-title":"J. Oral Pathol. Med."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"e15158","DOI":"10.7717\/peerj.15158","article-title":"Senescent epithelial cells remodel the microenvironment for the progression of oral submucous fibrosis through secreting TGF-\u03b21","volume":"11","author":"Wang","year":"2023","journal-title":"PeerJ"},{"key":"ref_215","unstructured":"IARC (2010). Ingested Nitrate and Nitrite, and Cyanobacterial Peptide Toxins. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, IARC."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.mrgentox.2011.10.002","article-title":"Microcystin-LR induced DNA damage in human peripheral blood lymphocytes","volume":"726","author":"Gajski","year":"2011","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"D\u00edez-Quijada, L., Hercog, K., \u0160tampar, M., Filipi\u010d, M., Came\u00e1n, A.M., Jos, \u00c1., and \u017degura, B. (2020). Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line. Toxins, 12.","DOI":"10.3390\/toxins12120778"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1007\/s00204-011-0716-z","article-title":"Genotoxic effects of the cyanobacterial hepatotoxin cylindrospermopsin in the HepG2 cell line","volume":"85","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"113632","DOI":"10.1016\/j.fct.2023.113632","article-title":"Evaluation of the genotoxic potential of acrylamide: Arguments for the derivation of a tolerable daily intake (TDI value)","volume":"173","author":"Guth","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1158\/1535-7163.MCT-21-0228","article-title":"Molecular Dosimetry of Temozolomide: Quantification of Critical Lesions, Correlation to Cell Death Responses, and Threshold Doses","volume":"20","author":"Stratenwerth","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/em.21834","article-title":"Does increase in DNA repair allow \u201cTolerance-to-Insult\u201d in chemical carcinogenesis? Skin tumor experiments with MGMT-overexpressing mice","volume":"55","author":"Becker","year":"2013","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/carcin\/bgv114","article-title":"DNA repair by MGMT, but not AAG, causes a threshold in alkylation-induced colorectal carcinogenesis","volume":"36","author":"Fahrer","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1093\/carcin\/bgg005","article-title":"Variability and regulation of O6-alkylguanine-DNA alkyltransferase","volume":"24","author":"Margison","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41586-021-03307-7","article-title":"The central role of DNA damage in the ageing process","volume":"592","author":"Schumacher","year":"2021","journal-title":"Nature"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"111587","DOI":"10.1016\/j.mad.2021.111587","article-title":"Recent advances in the discovery of senolytics","volume":"200","author":"Zhang","year":"2021","journal-title":"Mech. Ageing Dev."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Beltzig, L., Christmann, M., and Kaina, B. (2022). Abrogation of Cellular Senescence Induced by Temozolomide in Glioblastoma Cells: Search for Senolytics. Cells, 11.","DOI":"10.3390\/cells11162588"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2389\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:17:18Z","timestamp":1772774238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2389"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":226,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052389"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052389","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]}}}