{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:49:48Z","timestamp":1791355788379,"version":"4.3.1"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>We review the genotoxic effects of trace metal exposure and evaluate an efficient treatment strategy. Toxic metal(loid)s cause significant risks to animal health and ecosystems because of their toxicity and bioaccumulation potential. We then examine the mechanisms of genotoxicity, which include direct DNA damage, oxidative stress, epigenetic alterations, and interference with DNA repair mechanisms. This review highlights the health implications of toxic metal exposure: symptoms like increased cancer risks, reproductive and developmental toxicity, and chronic health disorders. Various assessment and biomonitoring techniques for toxic metal genotoxicity, including biomarkers like DNA adducts and chromosomal aberrations, and analytical methods such as the comet assay and PCR-based molecular assays, are discussed. We evaluate treatment strategies, including chelation therapy, antioxidant supplementation, and phytoremediation, emphasizing their efficacy and limitations. The importance of regulatory frameworks, public health interventions, and environmental remediation programs in mitigating toxic metal exposure is also discussed. We identify research gaps in understanding the long-term effects of low-dose chronic exposure and interactions between multiple toxic metals. This comprehensive review contributes to the field by synthesizing current knowledge on toxic metal genotoxicity and treatment strategies. We provide valuable insights for researchers, healthcare professionals, and policymakers toward the development of more effective prevention and intervention strategies. We emphasize challenges and future directions and highlight the importance of continued research in this critical area of public health and environmental science.<\/jats:p>","DOI":"10.3389\/ftox.2026.1906308","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:51:41Z","timestamp":1791352301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The genotoxic burden of toxic metals: bridging molecular mechanisms, biomonitoring, and multidisciplinary interventions"],"prefix":"10.3389","volume":"8","author":[{"given":"Sameera Reem","family":"Imthiaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suryapratap","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracy Anu","family":"Francis","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology, Vellore Institute of Technology","place":["Vellore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Vashishth","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology, Vellore Institute of Technology","place":["Vellore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5403","DOI":"10.1016\/j.sjbs.2021.05.068","article-title":"Assessment of DNA damage in relation to heavy metal induced oxidative stress in females with recurrent pregnancy loss (RPL)","volume":"28","author":"Alrashed","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1039\/B903049B","article-title":"Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium","volume":"1","author":"Arita","year":"2009","journal-title":"Metallomics Integr. Biometal Sci."},{"key":"B3","first-page":"1959","article-title":"Comparing conventional and advanced approaches for heavy metal removal in wastewater treatment: an In-Depth review emphasizing filter-based strategies","volume-title":"Polym. (Basel)","author":"Ayach","year":"2024"},{"key":"B4","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/J.JEEM.2012.07.006","article-title":"Impact of a randomized controlled trial in arsenic risk communication on household water-source choices in Bangladesh","volume":"65","author":"Bennear","year":"2012","journal-title":"J. Environ. Econ. Manag."},{"key":"B5","doi-asserted-by":"publisher","first-page":"464","DOI":"10.2174\/138920291506150106153336","article-title":"Send orders for reprints to reprints@benthamscience.ae epigenetic modifications due to heavy metals exposure in children liv-ing in polluted areas","volume":"15","author":"Bitto","year":"2014","journal-title":"Curr. Genomics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/s13148-021-01198-z","article-title":"Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals","volume":"13","author":"Bozack","year":"2021","journal-title":"Clin. Epigenetics"},{"key":"B7","unstructured":"Low level lead exposure harms children: a renewed call for primary prevention\n          \n          \n          2012"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1278185","DOI":"10.3389\/fpls.2023.1278185","article-title":"The role of epigenetic and epitranscriptomic modifications in plants exposed to non-essential metals","volume":"14","author":"Chmielowska-B\u0105k","year":"2023","journal-title":"Front. Plant Sci."},{"key":"B9","volume-title":"Toxic Metals and Oxidative Stress Part I: Mechanisms Involved in metal-induced Oxidative Damage","author":"Ercal","year":"2001"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.3892\/ijmm.2016.2728","article-title":"Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases","volume":"38","author":"Gangemi","year":"2016","journal-title":"Int. Journal Molecular Medicine"},{"key":"B11","first-page":"371","article-title":"Effects of green tea polyphenols against metal-induced genotoxic damage: underlying mechanistic pathways","volume-title":"J. Toxicol. Environ. Health. B Crit. Rev","author":"Garc\u00eda-Rodr\u00edguez","year":"2023"},{"key":"B12","first-page":"7297","article-title":"Sustainable mitigation of heavy metals from effluents: toxicity and fate with recent technological advancements","volume-title":"Bioengineered","author":"Gaur","year":"2021"},{"key":"B13","doi-asserted-by":"publisher","first-page":"125063","DOI":"10.1016\/J.CHEMOSPHERE.2019.125063","article-title":"Phyto-genotoxicity of arsenic contaminated soil from lakhimpur Kheri, India on Vicia faba L","volume":"241","author":"Gupta","year":"2020","journal-title":"Chemosphere"},{"key":"B14","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s10534-013-9644-2","article-title":"Mechanisms in cadmium-induced carcinogenicity: recent insights","volume":"26","author":"Hartwig","year":"2013","journal-title":"Biometals"},{"key":"B15","doi-asserted-by":"publisher","first-page":"4307","DOI":"10.3390\/IJERPH19074307","article-title":"Genotoxic effects of lead and their impact on the expression of DNA repair genes","volume":"19","author":"Hemmaphan","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1000235","DOI":"10.4172\/2167-0501.1000235","article-title":"DNA damage by heavy metals in animals and human beings: an overview","volume":"6","author":"Jadoon","year":"2017","journal-title":"Biochem. and Pharmacol. Open Access"},{"key":"B17","first-page":"60","article-title":"Toxicity, mechanism and health effects of some heavy metals","volume-title":"Interdiscip. Toxicol","author":"Jaishankar","year":"2014"},{"key":"B18","first-page":"29592","article-title":"Heavy metals and human health: mechanistic insight into toxicity and counter defense system of antioxidants","volume-title":"Int. J. Mol. Sci","author":"Jan","year":"2015"},{"key":"B20","doi-asserted-by":"publisher","first-page":"056002","DOI":"10.1289\/EHP3789","article-title":"DNA repair inhibition by toxic metal ions: mechanisms and implications for carcinogenesis","volume":"127","author":"Jiang","year":"2019","journal-title":"Environ. Health Perspect."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3769","DOI":"10.1021\/ES062717D","article-title":"Classification of heavy-metal toxicity by human DNA microarray analysis","volume":"41","author":"Kawata","year":"2007","journal-title":"Environ. Sci. and Technol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"227","DOI":"10.17582\/JOURNAL.PJAR\/2022\/35.1.227.239","article-title":"Phytoremediation of heavy metals from irrigation water \u2013 case study of hayatabad peshawar","volume":"35","author":"Khan","year":"2022","journal-title":"Pak. J. Agric. Res."},{"key":"B23","first-page":"2079","article-title":"The preventive and carcinogenic effect of metals on cancer: a systematic review","volume-title":"BMC Public Health","author":"Khoshakhlagh","year":"2024"},{"key":"B24","doi-asserted-by":"publisher","first-page":"232","DOI":"10.15430\/jcp.2015.20.4.232","article-title":"An overview of carcinogenic heavy metal: molecular toxicity mechanism and prevention","volume":"20","author":"Kim","year":"2015","journal-title":"J. Cancer Prev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/s1383-5718(98)00145-4","article-title":"Detection of genotoxic effects of heavy metal contaminated soils with plant bioassays","volume":"420","author":"Knasmuller","year":"1998","journal-title":"Mutat. Res."},{"key":"B26","first-page":"3","article-title":"Cellular pathologies and genotoxic effects arising secondary to heavy metal exposure: a review","volume-title":"Hum. Exp. Toxicol","author":"Kocadal","year":"2020"},{"key":"B27","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3390\/toxics13030167","article-title":"Effects of environmental non-essential toxic heavy metals on epigenetics during development","volume":"13","author":"Kurita","year":"2025","journal-title":"Toxics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1001\/JAMA.2013.2107","article-title":"Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial","volume":"309","author":"Lamas","year":"2013","journal-title":"JAMA"},{"key":"B29","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/j.mrgentox.2020.503231","article-title":"Induction of genotoxicity and mutagenic potential of heavy metals in Thai occupational workers","author":"Leelapongwattana","year":"2020","journal-title":"Mutat. Res. - Genet. Toxicol. Environ. Mutagen."},{"key":"B30","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/J.BBRC.2004.06.102","article-title":"Cadmium inhibits human DNA mismatch repair in vivo","volume":"321","author":"L\u00fctzen","year":"2004","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B31","first-page":"3003","article-title":"Heavy metal induced oxidative stress mitigation and ROS scavenging in plants","volume-title":"Plants (Basel)","author":"Mansoor","year":"2023"},{"key":"B32","doi-asserted-by":"publisher","first-page":"53","DOI":"10.59298\/NIJPP\/2025\/635358","article-title":"Environmental pollution and cancer: immunotoxic mechanisms and emerging therapeutic insights","volume":"6","author":"Mark","year":"2025","journal-title":"NEWPORT Int. J. PUBLIC HEALTH Pharm."},{"key":"B33","doi-asserted-by":"publisher","first-page":"820","DOI":"10.4161\/epi.6.7.16250","article-title":"Environmental epigenetics in metal exposure","volume":"6","author":"Martinez-Zamudio","year":"2011","journal-title":"Epigenetics"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e0151367","DOI":"10.1371\/journal.pone.0151367","article-title":"Heavy metal exposure influences double strand break DNA repair outcomes","volume":"11","author":"Morales","year":"2016","journal-title":"PLoS ONE"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2899","DOI":"10.1007\/S00204-022-03352-9","article-title":"Association between lead exposure and DNA damage (genotoxicity): systematic review and meta-analysis","volume":"96","author":"Nagaraju","year":"2022","journal-title":"Archives Toxicol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"27704","DOI":"10.1038\/s41598-025-12120-5","article-title":"Spatial assessment of heavy metal contamination in groundwater in the kadaladi region, Tamil Nadu, India","volume":"15","author":"Narayanan","year":"2025","journal-title":"Sci. Rep."},{"key":"B37","unstructured":"Hexavalent chromium compounds\n          \n          \n          2024"},{"key":"B38","volume-title":"Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures Risk Assessment Forum Technical Panel","year":"2000"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-87677-y","article-title":"Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure","volume":"11","author":"Nava-Rivera","year":"2021","journal-title":"Sci. Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"213","DOI":"10.4236\/gep.2023.117015","article-title":"GIS mapping, biomonitoring and distribution of heavy metal concentrations using neem (Azadirachta indica) bark in makurdi town, Benue state, Nigeria","volume":"11","author":"Ogli","year":"2023","journal-title":"J. Geoscience Environ. Prot."},{"key":"B41","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/J.TCM.2014.06.002","article-title":"Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients","volume":"24","author":"Peguero","year":"2014","journal-title":"Trends Cardiovasc. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"201","DOI":"10.3389\/fgene.2014.00201","article-title":"Incorporating epigenetic data into the risk assessment process for the toxic metals arsenic, cadmium, chromium, lead, and Mercury: strategies and challenges","volume":"5","author":"Ray","year":"2014","journal-title":"Front. Genetics"},{"key":"B43","volume-title":"United Nations Environment Programme Desiree Raquel Narvaez, United Nations Environment Programme Walker Smith","author":"Rees","year":"2020"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5487\/TR.2015.31.1.001","article-title":"Influence of toxicologically relevant metals on human epigenetic regulation","volume":"31","author":"Ryu","year":"2015","journal-title":"Toxicol. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3390\/ANTIOX10020277","article-title":"Abiotic stress and reactive oxygen species: generation, signaling, and defense mechanisms","volume":"10","author":"Sachdev","year":"2021","journal-title":"Antioxidants"},{"key":"B46","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.1172\/JCI80007","article-title":"Immunity, inflammation, and cancer: an eternal fight between good and evil","volume":"125","author":"Shalapour","year":"2015","journal-title":"J. Clinical Investigation"},{"key":"B47","doi-asserted-by":"publisher","first-page":"20143085","DOI":"10.1098\/RSPB.2014.3085","article-title":"Evolution of the immune system in humans from infancy to old age","volume":"282","author":"Simon","year":"2015","journal-title":"Proc. Biol. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.3390\/ANTIOX11122375","article-title":"Hexavalent-chromium-induced oxidative stress and the protective role of antioxidants against cellular toxicity","volume":"11","author":"Singh","year":"2022","journal-title":"Antioxidants"},{"key":"B49","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1007\/S10646-009-0313-6\/TABLES\/6","article-title":"Multivariate modeling of chromium-induced oxidative stress and biochemical changes in plants of pistia stratiotes L","volume":"18","author":"Sinha","year":"2009","journal-title":"Ecotoxicology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3390\/IJERPH13010088","article-title":"Cadmium chloride induces DNA damage and apoptosis of human liver carcinoma cells via oxidative stress","volume":"13","author":"Skipper","year":"2016","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B51","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/J.ECOLENG.2014.03.029","article-title":"Assessment of phytoremediation potential of native plants during the reclamation of an area affected by sewage sludge","volume":"69","author":"Suchkova","year":"2014","journal-title":"Ecol. Eng."},{"key":"B52","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1021\/acs.chemrestox.9b00464","article-title":"Molecular mechanisms of arsenic-induced disruption of DNA repair","volume":"33","author":"Tam","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/978-3-7643-8340-4_6","article-title":"Heavy metal toxicity and the environment","volume":"101","author":"Tchounwou","year":"2012","journal-title":"Exp. Suppl."},{"key":"B54","volume-title":"Arsenic Primer: Guidance on the Investigation and Mitigation of Arsenic Contamination","year":"2018"},{"key":"B55","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s13148-015-0130-0","article-title":"Epidemiologic evidence for association between adverse environmental exposures in early life and epigenetic variation: a potential link to disease susceptibility?","volume":"7","author":"Vaiserman","year":"2015","journal-title":"Clin. Epigenetics"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.2174\/0929867053764635","article-title":"Metals, toxicity and oxidative stress","volume":"12","author":"Valko","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"41","DOI":"10.4137\/BMI.S11456","article-title":"Oxidative stress and DNA damage induced by chromium in liver and kidney of goldfish, Carassius auratus","volume":"7","author":"Velma","year":"2013","journal-title":"Environ. Health Insights"},{"key":"B58","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2478\/cdem-2022-0006","article-title":"The biological monitoring as a source of information on environmental pollution with heavy metals","volume":"27","author":"Wac\u0142awek","year":"2022","journal-title":"Chem. Didact. Ecol. Metrol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e79699","DOI":"10.7759\/CUREUS.79699","article-title":"Role of antioxidant supplementation in enhancing chelation therapy for lead-induced oxidative stress in rats","volume":"17","author":"Waidande","year":"2025","journal-title":"Cureus"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e33853","DOI":"10.1371\/journal.pone.0033853","article-title":"Low-dose Cd induces hepatic gene hypermethylation, along with the persistent reduction of cell death and increase of cell proliferation in rats and mice","volume":"7","author":"Wang","year":"2012","journal-title":"PLOS ONE"},{"key":"B60","doi-asserted-by":"publisher","first-page":"695484","DOI":"10.3389\/fimmu.2021.695484","article-title":"Effects of cadmium exposure on the immune system and immunoregulation","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Immunology"},{"key":"B61","first-page":"245","article-title":"Blood lead levels in children aged 1\u20135 years \u2014 united States, 1999\u20132010","volume":"62","author":"Wheeler","year":"2013","journal-title":"MMWR. Morb. Mortal. Wkly. Rep."},{"key":"B62","volume-title":"Cadmium in drinking-water Background Document for Development of WHO Guidelines for drinking-water Quality","year":"2011"},{"key":"B63","doi-asserted-by":"publisher","first-page":"5100","DOI":"10.1021\/ACSOMEGA.3C07047\/ASSET\/IMAGES\/LARGE\/AO3C07047_0008.JPEG","article-title":"The toxicity of mercury and its chemical compounds: molecular mechanisms and environmental and human health implications: a comprehensive review","volume":"9","author":"Wu","year":"2024","journal-title":"ACS Omega"},{"key":"B64","first-page":"359","article-title":"Phytoremediation: a promising approach for revegetation of heavy metal-polluted land","volume-title":"Front. Plant Sci","author":"Yan","year":"2020"},{"key":"B65","first-page":"8526","article-title":"Environmental biomonitoring of heavy and toxic metals using honeybees and their products\u2014an overview of previous research","volume-title":"Sustainability","author":"Zavrtnik","year":"2024"},{"key":"B66","first-page":"552","article-title":"Dietary strategies for the treatment of cadmium and lead toxicity","volume-title":"Nutrients","author":"Zhai","year":"2015"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1367644","DOI":"10.3389\/fpubh.2024.1367644","article-title":"Association between heavy metals exposure and persistent infections: the mediating role of immune function","volume":"12","author":"Zhang","year":"2024","journal-title":"Front. Public Health"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.7150\/ijms.6308","article-title":"Cadmium induced cell apoptosis, DNA damage, De-creased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells","volume":"10","author":"Zhou","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/J.MRFMMM.2011.02.015","article-title":"Reactive oxygen species (ROS)--induced genetic and epigenetic alterations in human carcinogenesis","volume":"711","author":"Ziech","year":"2011","journal-title":"Mutat. Res."}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1906308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:51:45Z","timestamp":1791352305000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2026.1906308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":69,"alternative-id":["10.3389\/ftox.2026.1906308"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2026.1906308","relation":{},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"1906308"}}