{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:08:54Z","timestamp":1791277734582,"version":"4.1.0"},"reference-count":137,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2011,12,20]],"date-time":"2011-12-20T00:00:00Z","timestamp":1324339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system\u2019s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others) with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase) as well as certain regulatory factors, including AP-1, NF-\u03baB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression.<\/jats:p>","DOI":"10.3390\/ijms12129576","type":"journal-article","created":{"date-parts":[[2011,12,20]],"date-time":"2011-12-20T16:40:37Z","timestamp":1324399237000},"page":"9576-9595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":152,"title":["Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers"],"prefix":"10.3390","volume":"12","author":[{"given":"Preeyaporn","family":"Koedrith","sequence":"first","affiliation":[{"name":"Department of Life Science, Dongguk University, 30 Pildong-ro 1-gil (26 Pildong 3-ga), Jung-gu, Seoul 100-715, Korea"},{"name":"Institute of Environmental Medicine for Green Chemistry, Dongguk University, 30 Pildong-ro 1-gil (26 Pildong 3-ga), Jung-gu, Seoul 100-715, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Rok","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University, 30 Pildong-ro 1-gil (26 Pildong 3-ga), Jung-gu, Seoul 100-715, Korea"},{"name":"Institute of Environmental Medicine for Green Chemistry, Dongguk University, 30 Pildong-ro 1-gil (26 Pildong 3-ga), Jung-gu, Seoul 100-715, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2011,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00204-008-0313-y","article-title":"Carcinogenic metal compounds: Recent insight into molecular and cellular mechanisms","volume":"82","author":"Beyersmann","year":"2008","journal-title":"Arch. Toxicol"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1089\/15230860152542970","article-title":"Zinc finger proteins as potential targets for toxic metal ions: Differential effects on structure and function","volume":"3","author":"Hartwig","year":"2001","journal-title":"Antioxid. Redox Signal"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1039\/a808849g","article-title":"Relevance of reactivity determinants to exposure assessment and biological monitoring of the elements","volume":"1","author":"Nieboer","year":"1999","journal-title":"J. Environ. Monit"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tox.2011.03.001","article-title":"Advances in metal-induced oxidative stress and human disease","volume":"283","author":"Jomova","year":"2011","journal-title":"Toxicology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1357-2725(01)00143-1","article-title":"Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation\/death","volume":"34","author":"Asenjo","year":"2002","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00204-008-0304-z","article-title":"Intracellular redox status and oxidative stress: Implications for cell proliferation, apoptosis, and carcinogenesis","volume":"82","author":"Segura","year":"2008","journal-title":"Arch. Toxicol"},{"key":"ref_7","first-page":"219","article-title":"Studies on free radicals, antioxidants, and co-factors","volume":"2","author":"Rahman","year":"2007","journal-title":"Clin. Interv. Aging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.2174\/0929867043365323","article-title":"Oxidative stress and cell signalling","volume":"11","author":"Poli","year":"2004","journal-title":"Curr. Med. Chem"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1023\/B:MCBI.0000049134.69131.89","article-title":"Role of oxygen radicals in DNA damage and cancer incidence","volume":"266","author":"Valko","year":"2004","journal-title":"Mol. Cell. Biochem"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2005.12.009","article-title":"Free radicals, metals and antioxidants in oxidative stress-induced cancer","volume":"160","author":"Valko","year":"2006","journal-title":"Chem. Biol. Interact"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10873","DOI":"10.1016\/S0021-9258(17)44357-2","article-title":"Ferritin. Binding of beryllium and other divalent metal ions","volume":"258","author":"Price","year":"1983","journal-title":"J. Biol. Chem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1006\/abbi.1997.0197","article-title":"Enzyme activity alteration by cadmium administration to rats: The possibility of iron involvement in lipid peroxidation","volume":"346","author":"Casalino","year":"1997","journal-title":"Arch. Biochem. Biophys"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s13273-011-0009-x","article-title":"The protective role of Nrf2 in cadmium-induced DNA damage","volume":"7","author":"Park","year":"2011","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0890-6238(03)00100-X","article-title":"Cadmium-induced damage to primary cultures of rat Leydig cells","volume":"17","author":"Yang","year":"2003","journal-title":"Reprod. Toxicol"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/ijc.20736","article-title":"Cadmium-induced malignant transformation in rat liver cells: Role of aberrant oncogene expression and minimal role of oxidative stress","volume":"114","author":"Qu","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.toxlet.2005.10.018","article-title":"Damage of zinc fingers in DNA repair proteins, a novel molecular mechanism in carcinogenesis","volume":"162","author":"Bal","year":"2006","journal-title":"Toxicol. Lett"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1089\/ham.2008.1028","article-title":"Hypoxic preconditioning with cobalt attenuates hypobaric hypoxia-induced oxidative damage in rat lungs","volume":"10","author":"Shukla","year":"2009","journal-title":"High Alt. Med. Biol"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.cellsig.2007.04.009","article-title":"Oxyl radicals, redox-sensitive signallingcascades and antioxidants","volume":"19","author":"Genestra","year":"2007","journal-title":"Cell. Signal"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s13273-010-0003-8","article-title":"Effects of blood lead concentration on intelligence and personality in school children","volume":"6","author":"Kim","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1080\/10408440600845619","article-title":"The toxicology of mercury and its chemical compounds","volume":"36","author":"Clarkson","year":"2006","journal-title":"Crit. Rev. Toxicol"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s13273-010-0047-9","article-title":"Biomonitoring of urinary mercury in Korean school children","volume":"6","author":"Kim","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1177\/039463200702000404","article-title":"Metallic nanoparticles exhibit paradoxical effects on oxidative stress and pro-inflammatory response in endothelial cells in vitro","volume":"20","author":"Peters","year":"2007","journal-title":"Int. J. Immunopathol. Pharmacol"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1021\/tx2000015","article-title":"Genotoxicity evaluation of nanomaterials: DNA damage, micronuclei, and 8-hydroxy-2-deoxyguanosine induced by magnetic doped CdSe quantum dots in male mice","volume":"24","author":"Khalil","year":"2011","journal-title":"Chem. Res. Toxicol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s13273-010-0041-2","article-title":"Particle-induced expression of SF20\/IL25 is mediated by reactive oxygen species and NF-\u03baB in alveolar macrophages","volume":"6","author":"Kim","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s13273-010-0018-1","article-title":"Cytotoxicity and genotoxicity of nano-silver in mammalian cell lines","volume":"6","author":"Kim","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s13273-011-0010-4","article-title":"Comparison of cellular effects of titanium dioxide nanoparticles with different photocatalytic potential in human keratinocyte, HaCaT cells","volume":"7","author":"Park","year":"2011","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s13273-010-0002-9","article-title":"The effect of nano-scale Zn-doped TiO2 and pure TiO2 particles on Hydra magnipapillata","volume":"6","author":"Yeo","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s13273-010-0055-9","article-title":"Proteomic profiling of the differentially expressed proteins by TiO2 nanoparticles in mouse kidney","volume":"6","author":"Jeon","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s13273-010-0013-6","article-title":"Gene expression in zebrafish embryos following exposure to TiO2 nanoparticles","volume":"6","author":"Yeo","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_30","first-page":"311","article-title":"Exposing zebrafish to silver nanoparticles during caudal fin regeneration disrupts caudal fin growth and p53 signaling","volume":"4","author":"Yeo","year":"2008","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_31","first-page":"23","article-title":"Comparison of the effects of nano-silver antibacterial coating and silver ions on zebrafish embryogenesis","volume":"5","author":"Yeo","year":"2009","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0378-4274(01)00482-9","article-title":"Interactions by carcinogenic metal compounds with DNA repair processes: Toxicological implications","volume":"127","author":"Hartwig","year":"2002","journal-title":"Toxicol. Lett"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0921-8777(96)00052-3","article-title":"Cobalt(II) inhibits the incision and the polymerization step of nucleotide excision repair in human fibroblasts","volume":"383","author":"Kasten","year":"1997","journal-title":"Mutat. Res"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s002160050909","article-title":"Disruptions of DNA repair processes by carcinogenic metal compounds","volume":"361","author":"Hartwig","year":"1998","journal-title":"Fresenius J. Anal. Chem"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1093\/carcin\/17.12.2779","article-title":"Negative interference of metal(II) ions with nucleotide excision repair in human cell-free extracts","volume":"17","author":"Calsoul","year":"1996","journal-title":"Carcinogenesis"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1021\/tx900444w","article-title":"Genotoxicity of soluble and particulate cadmium compounds: Impact on oxidative DNA damage and nucleotide excision repair","volume":"23","author":"Schwerdtle","year":"2010","journal-title":"Chem. Res. Toxicol"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.tox.2003.08.004","article-title":"Modulation of DNA repair processes by arsenic and selenium compounds","volume":"193","author":"Hartwig","year":"2003a","journal-title":"Toxicology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ijc.10911","article-title":"Very low concentrations of arsenite suppress poly(ADP-ribosyl)ation in mammalian cells","volume":"104","author":"Hartwig","year":"2003b","journal-title":"Int. J. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.dnarep.2003.09.001","article-title":"Arsenite and its biomethylated metabolites interfere with the formation and repair of stable BPDE-induced DNA adducts in human cells and impair XPAzf and Fpg","volume":"2","author":"Schwerdtle","year":"2003","journal-title":"DNA Repair"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14282","DOI":"10.1021\/bi048560o","article-title":"Chromium(VI) enhances (\u00b1)-anti-7\u03b2,8\u03b1-dihydroxy-9\u03b1,10\u03b1-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-induced cytotoxicity and mutagenicity in mammalian cells through its inhibitory effect on nucleotide excision repair","volume":"43","author":"Hu","year":"2004","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1158\/1055-9965.EPI-04-0295","article-title":"Interindividual variability in response to sodium dichromate-induced oxidative DNA damage: Role of the Ser326Cys polymorphism in the DNA repair protein of 8-oxo-7,8-dihydro-2\u2032-deoxyguanosine DNA glycosylase 1","volume":"14","author":"Lee","year":"2005","journal-title":"Cancer Epidermiol. Biomark. Prev"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1093\/carcin\/21.11.1977","article-title":"Identification of single nucleotide polymorphisms in human DNA repair genes","volume":"21","author":"Ford","year":"2000","journal-title":"Carcinogenesis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.mrfmmm.2005.03.033","article-title":"Modulation of oxidative mutagenesis and carcinogenesis by polymorphic forms of human DNA repair enzymes","volume":"591","author":"Nohmi","year":"2005","journal-title":"Mutat. Res"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.2174\/0929867043365323","article-title":"Oxidative stress and cell signalling","volume":"11","author":"Poli","year":"2004","journal-title":"Curr. Med. Chem"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"L1005","DOI":"10.1152\/ajplung.2000.279.6.L1005","article-title":"Reactive oxygen species in cell signaling","volume":"279","author":"Thannickal","year":"2000","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s001090050063","article-title":"Transcription factor AP-1 regulations by mitogen-activated protein kinase signal transduction pathways","volume":"74","author":"Whitmarsh","year":"1996","journal-title":"J. Mol. Med"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13422","DOI":"10.1074\/jbc.271.23.13422","article-title":"Role of oxidants and antioxidants in the induction of AP-1, NF-kappa B, and glutathione S-transferase gene expression","volume":"271","author":"Pinkus","year":"1996","journal-title":"J. Biol. Chem"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s10555-005-1579-7","article-title":"Role of nuclear factor-kappa B in melanoma","volume":"24","author":"Amiri","year":"2005","journal-title":"Cancer Metastasis Rev"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"357","DOI":"10.2174\/0929867053363180","article-title":"NF-kappa B in human disease: Current inhibitors and prospects for de novo structure based design of inhibitors","volume":"12","author":"Pande","year":"2005","journal-title":"Curr. Med. Chem"},{"key":"ref_50","first-page":"145","article-title":"Free radicals, antioxidants, and the immune system","volume":"30","author":"Knight","year":"2000","journal-title":"Ann. Clin. Lab. Sci"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1042\/BJ20050078","article-title":"Mitochondrial reactive oxygen species regulate the temporal activation of nuclear factor kappa B to modulate tumour necrosis factor-induced apoptosis: Evidence from mitochondria-targeted antioxidants","volume":"389","author":"Hughes","year":"2005","journal-title":"Biochem. J"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1126\/science.1905840","article-title":"p53 mutations in human cancer","volume":"253","author":"Hollstein","year":"1991","journal-title":"Science"},{"key":"ref_53","first-page":"218","article-title":"Altered p53 gene structure and expression in human epithelial cells after exposure to nickel","volume":"52","author":"Maehle","year":"1992","journal-title":"Cancer Res"},{"key":"ref_54","first-page":"247","article-title":"TP53 mutation specta and load: A tool for generating hypotheses on the etiology of cancer","volume":"157","author":"Olivier","year":"2004","journal-title":"IARC Sci. Publ"},{"key":"ref_55","first-page":"3053","article-title":"Arsenic induces apoptosis through a c-Jun NH2-terminal kinase-dependent, p53-independent pathway","volume":"59","author":"Huang","year":"1999","journal-title":"Cancer Res"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/carcin\/22.5.757","article-title":"Mechanisms of Cr(VI)-induced p53 activation: The role of phosphorylation, mdm2 and ERK","volume":"22","author":"Wang","year":"2001","journal-title":"Carcinogenesis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/ncb816","article-title":"The role of FAT transcription factors in integrin-mediated carcinoma invasion","volume":"4","author":"Jauliac","year":"2002","journal-title":"Nat. Cell Biol"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1146\/annurev.immunol.15.1.707","article-title":"Transcription factors of the NFAT family: Regulation and function","volume":"15","author":"Rao","year":"1997","journal-title":"Ann. Rev. Immunol"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1126\/science.278.5343.1638","article-title":"Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway","volume":"278","author":"Chow","year":"1997","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1016\/j.freeradbiomed.2004.09.010","article-title":"Metal-induced oxidative stress and signal transduction","volume":"37","author":"Leonard","year":"2004","journal-title":"Free Radic. Biol. Med"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1152\/jappl.2000.88.4.1474","article-title":"HIF-1: Mediator of physiological and pathophysiological responses to hypoxia","volume":"88","author":"Semenza","year":"2000","journal-title":"J. Appl. Physiol"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"45041","DOI":"10.1074\/jbc.M202775200","article-title":"p38 signaling-mediated hypoxia-inducible factor 1 alpha and vascular endothelial growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells","volume":"277","author":"Gao","year":"2002","journal-title":"J. Biol. Chem"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1021\/tx700198a","article-title":"Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: Nickel, arsenic, and chromium","volume":"21","author":"Salnikow","year":"2008","journal-title":"Chem. Res. Toxicol"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4682","DOI":"10.1021\/cr800556u","article-title":"Coordination dynamics of zinc in proteins","volume":"109","author":"Maret","year":"2009","journal-title":"Chem. Rev"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1021\/cr0206263","article-title":"Synthetic analogues relevant to the structure and function of zinc enzymes","volume":"104","author":"Parkin","year":"2004","journal-title":"Chem. Rev"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1039\/c0mt00070a","article-title":"Zinc finger proteins as templates for metal ion exchange and ligan reactivity. Chemical and biological consequences","volume":"2","author":"Quintal","year":"2011","journal-title":"Metallomics"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.jinorgbio.2009.07.002","article-title":"Zinc finger proteins as templates for metal ion exchange: Substitution effects on the C-finger of HIV nucleocapsid NCp7 using M (chelate) species (M = Pt, Pd, Au)","volume":"103","author":"Mangrum","year":"2009","journal-title":"J. Inorg. Biochem"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/S0278-6915(02)00043-1","article-title":"Interference by toxic metal ions with zinc-dependent proteins involved in maintaining genomic stability","volume":"40","author":"Hartwig","year":"2002","journal-title":"Food Chem. Toxicol"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1089\/15230860152542970","article-title":"Zinc finger proteins as potential targets for toxic metal ions: Differential effects on structure and function","volume":"3","author":"Hartwig","year":"2001","journal-title":"Antioxid. Redox Signal"},{"key":"ref_70","first-page":"267","article-title":"Finger-loops, oncogenes, and metals. Claude Passmore Brown Memorial Lecture","volume":"18","author":"Sunderman","year":"1988","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"12182","DOI":"10.1016\/S0021-9258(19)49821-9","article-title":"Mutational analysis of the structure and function of the xerodermapigmentosum group A complementing protein","volume":"267","author":"Miyamoto","year":"1992","journal-title":"J. Biol. Chem"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.1093\/emboj\/cdg489","article-title":"The comings and goings of nucleotide excision repair factors on damaged DNA","volume":"22","author":"Riedl","year":"2003","journal-title":"EMBO J"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0921-8777(94)90034-5","article-title":"The XPA protein a zinc metalloprotein with an ability to recognize various kinds of DNA damage","volume":"315","author":"Asahina","year":"1994","journal-title":"Mutat. Res"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"12096","DOI":"10.1021\/bi00096a021","article-title":"Preferential binding of the xerodermapigmentosum group A complementing protein to damaged DNA","volume":"32","author":"Jones","year":"1993","journal-title":"Biochemistry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1002\/j.1460-2075.1991.tb04961.x","article-title":"Complementation of DNA repair in xerodermapigmentosum group A cell extracts by a protein with affinity for damaged DNA","volume":"10","author":"Robins","year":"1991","journal-title":"EMBO J"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1093\/carcin\/21.11.2097","article-title":"Differential effects of toxic metal compounds on the activities of Fpg and XPA, two zinc finger proteins involved in DNA repair","volume":"21","author":"Asmuss","year":"2000","journal-title":"Carcinogenesis"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1021\/tx025639q","article-title":"Mechanism of nickel assault on the zinc finger of DNA repair protein XPA","volume":"16","author":"Bal","year":"2003","journal-title":"Chem. Res. Toxicol"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1021\/tx049842s","article-title":"Co(II) and Cd(II) substitute for Zn(II) in the zinc finger derived from the DNA repair protein XPA, demonstrating a variety of potential mechanisms of toxicity","volume":"17","author":"Kopera","year":"2004","journal-title":"Chem. Res. Toxicol"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1073\/pnas.87.8.2990","article-title":"The second zinc-finger domain of poly(ADP-ribose) polymerase determines specificity for single-stranded breaks in DNA","volume":"87","author":"Gradwohl","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1101\/gad.1331805","article-title":"Poly(ADP-ribosyl)ation by PARP-1: \u2018PAR-laying\u2019 NAD(+) into a nuclear signal","volume":"19","author":"Kim","year":"2005","journal-title":"Genes Dev"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1083\/jcb.150.2.293","article-title":"A fast signal-induced activation of poly(ADP-ribose) polymerase: A novel downstream target of phospholipase C","volume":"150","author":"Homburg","year":"2000","journal-title":"J. Cell Biol"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1021\/jm2000135","article-title":"Metal-based inhibition of poly(ADP-ribose) polymerase-the guardian angel of DNA","volume":"54","author":"Mendes","year":"2011","journal-title":"J. Med. Chem"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0968-0004(94)90280-1","article-title":"Poly(ADP-ribose) polymerase-A molecular nick-sensor","volume":"19","year":"1994","journal-title":"Trends Biochem. Sci"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0027-5107(01)00111-7","article-title":"Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death","volume":"477","author":"Herceg","year":"2001","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0921-8777(00)00016-1","article-title":"Poly(ADP-ribosylation) reactions: From DNA damage and stress signalling to cell death","volume":"460","author":"Shall","year":"2000","journal-title":"Mutat. Res"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S1383-5742(97)00011-2","article-title":"Inhibition of poly(ADP-ribose) polymerase by arsenite","volume":"386","author":"Yager","year":"1997","journal-title":"Mutat. Res"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1089\/15230860152542961","article-title":"Zinc binding and redox control of p53 structure and function","volume":"3","author":"Hainaut","year":"2001","journal-title":"Antioxid. Redox Signal"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0065-230X(08)60785-X","article-title":"p53 and human cancer: The first ten thousand mutations","volume":"77","author":"Hainaut","year":"1999","journal-title":"Adv. Cancer Res"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0006-2952(99)00297-X","article-title":"Redox signalling and transition metals in the control of p53 pathway","volume":"59","author":"Richard","year":"2000","journal-title":"Biochem. Pharmacol"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1158\/1535-7163.MCT-06-0472","article-title":"Chemotherapeutic selectivity conferred by selenium: A role for p53-dependent DNA repair","volume":"6","author":"Fischer","year":"2007","journal-title":"Mol. Cancer Ther"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/biof.81","article-title":"Current issues of selenium in cancer chemoprevention","volume":"36","author":"Jung","year":"2010","journal-title":"Biofactors"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1089\/jmf.2007.0709","article-title":"Enhancement of methylmethanesulfonate-induced based excision repair in the presence of selenomethionine on p53-dependent pathway","volume":"12","author":"Jung","year":"2009","journal-title":"J. Med. Food"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"14548","DOI":"10.1073\/pnas.212319799","article-title":"Selenomethionine regulation of p53 by a ref 1-dependent redox mechanism","volume":"99","author":"Seo","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1038\/sj.onc.1205468","article-title":"Selenomethionine induction of DNA repair response in human fibroblasts","volume":"21","author":"Seo","year":"2002","journal-title":"Oncogene"},{"key":"ref_95","first-page":"1401","article-title":"Selenium compounds regulate p53 by common and distinctive mechanisms","volume":"24","author":"Smith","year":"2004","journal-title":"Anti-Cancer Res"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1038\/sj.onc.1202710","article-title":"Effect of transition metals on binding of p53 protein to supercoiled DNA and to consensus sequence in DNA fragments","volume":"18","author":"Palecek","year":"1999","journal-title":"Oncogene"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"31663","DOI":"10.1074\/jbc.274.44.31663","article-title":"Cadmium induces conformational modifications of wild-type p53 and suppress p53 response to DNA damage in cultured cells","volume":"274","author":"Meplan","year":"1999","journal-title":"J. Biol. Chem"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0027-5107(02)00003-9","article-title":"Attenuation of DNA polymerase-dependent base excision repair and increased DMS-induced mutagenicity in aged mice","volume":"500","author":"Cabelof","year":"2002","journal-title":"Mutat. Res"},{"key":"ref_99","first-page":"18425","article-title":"Development of quantitative DNA cleavage assay for XPG endonuclease activity using endogenous nuclear proteins in human cell lines","volume":"279","author":"Koedrith","year":"2004","journal-title":"Oncol. Rep"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0009-9120(99)00075-2","article-title":"Antioxidant enzymes and human diseases","volume":"32","author":"Mates","year":"1999","journal-title":"Clin. Biochem"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/S0891-5849(98)00302-5","article-title":"Can antioxidant vitamins materially reduce oxidative damage in humans?","volume":"26","author":"McCall","year":"1999","journal-title":"Free Radic. Biol. Med"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1093\/jn\/135.5.969","article-title":"Nutritional, dietary and post-prandial oxidative stress","volume":"135","author":"Sies","year":"2005","journal-title":"J. Nutr"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0076-6879(90)86093-B","article-title":"Role of free radicals and catalytic metal-ions in human disease-an overview","volume":"186","author":"Halliwell","year":"1990","journal-title":"Methods Enzymol"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s002040100240","article-title":"Effects on levels of glutathione and some related enzymes in tissues after an acute exposure in rats and their relationship to dietary protein deficiency","volume":"75","author":"Maiti","year":"2001","journal-title":"Arch. Toxicol"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/107691800317283662","article-title":"Toxic mechanism of cadmium exposure on cardiac tissue","volume":"19","author":"Novelli","year":"2000","journal-title":"Toxic Subst. Mech"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"563","DOI":"10.33549\/physiolres.930359","article-title":"Protective influence of vitamin E on antioxidant defense system in the blood of rats treated with cadmium","volume":"52","author":"Ognjanovic","year":"2003","journal-title":"Physiol. Res"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.scitotenv.2004.12.019","article-title":"Environmental exposure to lead and its correlation with biochemical indices in children","volume":"346","author":"Ahamed","year":"2005","journal-title":"Sci. Total Environ"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/009841000156916","article-title":"Developmental toxicity of lead-contaminated sediment in Canada geese (Branta canadensis)","volume":"59","author":"Hoffman","year":"2000","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.phrs.2009.02.011","article-title":"Mercury and human genotoxicity: Critical considerations and possible molecular mechanisms","volume":"60","author":"Pereira","year":"2009","journal-title":"Pharmacol. Res"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S1383-5718(97)00081-8","article-title":"Distinct genotoxicity of phenylmercury acetate in human lymphocytes as compared with other mercury compounds","volume":"392","author":"Lee","year":"1997","journal-title":"Mutat. Res"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.envres.2007.08.007","article-title":"Mercury exposure and antioxidant defenses in women: A comparative study in the Amazon","volume":"107","author":"Pinheiro","year":"2008","journal-title":"Environ. Res"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S1016-8478(23)13017-2","article-title":"Vitamin C and vitamin E protect the rat testes from cadmium-induced reactive oxygen species","volume":"17","author":"Gupta","year":"2004","journal-title":"Mol. Cells"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1023\/A:1010903130693","article-title":"Induction of lipid peroxidation in hamster organs by the carcinogen cadmium: Melioration by melatonin","volume":"17","author":"Karbownik","year":"2001","journal-title":"Cell Biol. Toxicol"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s13273-010-0019-0","article-title":"Heme oxygenase-1 mediated protective effect of methyl gallate on cadmium-induced cytotoxicity in cultured mouse mesangial cells","volume":"6","author":"Cha","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s13273-010-0022-5","article-title":"Influence of quercetin on the physiological response to cadmium stress in olive flounder, Paralichthysolivaceus: Effects on hematological and biochemical parameters","volume":"6","author":"Park","year":"2010","journal-title":"Mol. Cell. Toxicol"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1080\/10715760802350904","article-title":"The oxidation of glutathione by cobalt\/tungsten carbide contributes to hard metal-induced oxidative stress","volume":"42","author":"Fenoglio","year":"2008","journal-title":"Free Radic. Res"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"40337","DOI":"10.1074\/jbc.M403057200","article-title":"Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress","volume":"279","author":"Salnikow","year":"2004","journal-title":"J. Biol. Chem"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/15459620903349073","article-title":"Comparison of free radical generation by pre- and post-sintered cemented carbide particles","volume":"7","author":"Stefaniak","year":"2010","journal-title":"J. Occup. Environ. Hyg"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"12529","DOI":"10.1021\/bi020452j","article-title":"Critical role of chromium (Cr)-DNA interactions in the formation of Cr-induced polymerase arresting lesions","volume":"41","author":"Mandel","year":"2002","journal-title":"Biochemistry"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1021\/bi011942z","article-title":"Carcinogenic chromium(VI) induces cross-linking of vitamin C to DNA in vitro and in human lung 549 cells","volume":"41","author":"Quievryn","year":"2002","journal-title":"Biochemistry"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1021\/bi0271547","article-title":"Genotoxicity and mutagenicity of chromium(VI)\/ascorbate-generated DNA adducts in human and bacterial cells","volume":"42","author":"Quievryn","year":"2003","journal-title":"Biochemistry"},{"key":"ref_122","first-page":"169","article-title":"Mechanisms of chromium metabolism and genotoxicity","volume":"7","author":"Wetterhahn","year":"1989","journal-title":"Life Chem. Rep"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0048-9697(99)00548-3","article-title":"Effect of lead concentration on the level of glutathione, glutathione S-transferase, reductase and peroxidase in human blood","volume":"248","author":"Hunaiti","year":"2000","journal-title":"Sci. Total Environ"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free radicals and antioxidants in normal physiological functions and human disease","volume":"39","author":"Valko","year":"2007","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0890-6238(98)00030-6","article-title":"The effect of zinc supplementation on the effects of lead in the rat testis","volume":"12","author":"Batra","year":"1998","journal-title":"Reprod. Toxicol"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/(SICI)1099-0461(1998)12:6<345::AID-JBT4>3.0.CO;2-V","article-title":"Role of selenium against lead toxicity in male rats","volume":"12","author":"Othman","year":"1998","journal-title":"J. Biochem. Mol. Toxicol"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0300-483X(02)00223-8","article-title":"Lead induced oxidative damage and its response to combined administration of alpha-lipoic acid and succimers in rats","volume":"177","author":"Pande","year":"2002","journal-title":"Toxicology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/mutage\/15.6.525","article-title":"Mutagenicity of mercury chloride and mechanisms of cellular defence: The role of metal-binding proteins","volume":"15","author":"Schurz","year":"2000","journal-title":"Mutagenesis"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1590\/S0100-879X2006000300013","article-title":"Methylmercury intoxication activates nitric oxide synthase in chick retinal cell culture","volume":"39","author":"Herculano","year":"2006","journal-title":"Braz. J. Med. Biol. Res"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0887-2333(01)00081-9","article-title":"Role of ascorbic acid on mercuric chloride-induced genotoxicity in human blood cultures","volume":"15","author":"Rao","year":"2001","journal-title":"Toxicol. In Vitro"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.envres.2007.01.012","article-title":"Epidemiologic confirmation that fruit consumption influences mercury exposure in riparian communities in the Brazilian Amazon","volume":"105","author":"Passos","year":"2007","journal-title":"Environ. Res"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/annonc\/mdp286","article-title":"Effects of antioxidant supplements on cancer prevention: Meta-analysis of randomized controlled trials","volume":"21","author":"Myung","year":"2010","journal-title":"Ann. Oncol"},{"key":"ref_133","first-page":"127","article-title":"Mercury exposure: Medical and public health issues","volume":"116","author":"Mahaffey","year":"2005","journal-title":"Trans. Am. Clin. Climatol. Assoc"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.scitotenv.2005.01.023","article-title":"Biological monitoring of mercury exposure in individuals referred to a toxicological center in Venezuela","volume":"354","author":"Rojas","year":"2006","journal-title":"Sci. Total Environ"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1080\/08035250600886157","article-title":"Children\u2019s health and mercury exposure","volume":"95","author":"Ronchetti","year":"2006","journal-title":"Acta Paediatr. Suppl"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/tox.10116","article-title":"Environmental exposure to mercury and its toxicopathologic implications for public health","volume":"18","author":"Tchounwou","year":"2003","journal-title":"Environ. Toxicol"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.jnutbio.2004.07.005","article-title":"Zinc deficiency, DNA damage and cancer risk","volume":"15","author":"Ho","year":"2004","journal-title":"J. Nutr. Biochem"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/12\/12\/9576\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:58:25Z","timestamp":1760219905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/12\/12\/9576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,20]]},"references-count":137,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2011,12]]}},"alternative-id":["ijms12129576"],"URL":"https:\/\/doi.org\/10.3390\/ijms12129576","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,20]]}}}