Environmental toxicants--induced epigenetic alterations and their reversers

Our plain-English summary of Environmental toxicants--induced epigenetic alterations and their reversers, by M. Kim, M. Bae, H. Na, et al (Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews, 2012).

The study

• Authors: M. Kim, M. Bae, H. Na, M. Yang
• Journal: Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews
• Published: 2012;30(4):323-67
• Type of article: Review
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Epigenetics has been emphasized in the postgenome era to clarify obscure health risks of environmental toxicants including endocrine disrupting chemicals (EDCs). In addition, mixed exposure in real life can modify health consequences of the toxicants. Particularly, some nutritional and dietary materials modify individual susceptibility through changes in the epigenome. Therefore, we focused on some environmental toxicants that induce epigenetic alterations, and introduced chemopreventive materials to reverse the toxicants-induced epigenetic alterations. Methodologically, we used global and specific DNA methylation as epigenetic end points and searched epigenetic modulators in food. We reviewed various epigenetic end points induced by environmental toxicants including alcohol, asbestos, nanomaterials, benzene, EDCs, metals, and ionizing radiation. The epigenetic end points can be summarized into global hypomethylation and specific hypermethylation at diverse tumor suppress genes. Exposure timing, dose, sex, or organ specificity should be considered to use the epigenetic end points as biomarkers for exposure to the epimutagenic toxicants. Particularly, neonatal exposure to the epimutagens can influence their future adult health because of characteristics of the epimutagens, which disrupt epigenetic regulation in imprinting, organogenesis, development, etc. Considering interaction between epimutagenic toxicants and their reversers in food, we suggest that multiple exposures to them can alleviate or mask epigenetic toxicity in real life. Our present review provides useful information to find new end points of environmental toxicants and to prevention from environment-related diseases.

In plain English

This article was a review, not a new study. The authors surveyed published research on how environmental toxicants change DNA methylation, a chemical tagging of genes that can switch them off. The toxicants covered were alcohol, asbestos, nanomaterials, benzene, endocrine disrupting chemicals, metals and ionizing radiation. The authors also reviewed food components reported to reverse such changes. In the asbestos section, the review described other researchers' work on malignant pleural mesothelioma. Those studies reported that methylation silencing of tumor suppressor genes, including APC, CDKN2A, CDKN2B, HPPBP1 and RASSF1, was significantly associated with asbestos exposure. One reported an association between the period of asbestos exposure and methylation of such genes. Another linked methylation of the metallothionein genes MT1A and MT2A with asbestos burden. One study found mesothelin (MSLN) promoter methylation higher in normal pleura than in tumor tissue. Asbestos fiber types were not named. Across all toxicants, the authors summarized the changes as overall loss of methylation together with gain of methylation at specific tumor suppressor genes. The authors suggested that mixed exposure to toxicants and food-based reversers could ease or mask epigenetic toxicity in real life.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies (cell, animal and human) on toxicant-induced DNA methylation changes and dietary modulators
• Who was studied: No new population was studied. The review drew on previously published studies by other researchers. The asbestos section cited studies of malignant pleural mesothelioma tumors, pleura and pleural fluid.
• Exposure: Environmental toxicants: alcohol, asbestos (no fiber types specified), nanomaterials, benzene, endocrine disrupting chemicals, metals and ionizing radiation. Food-based modulators were also reviewed: methyl donor nutrients, dietary polyphenols, lycopene, vitamin D and selenium.
• Main results:
  • Overall, the authors summarized the reviewed epigenetic changes as global loss of methylation (hypomethylation) and gain of methylation (hypermethylation) at specific tumor suppressor genes.
  • Cited studies by Christensen and colleagues reported a significant association between asbestos exposure and methylation silencing of tumor suppressor genes in malignant pleural mesothelioma. The genes named were APC, CDKN2A, CDKN2B, HPPBP1 and RASSF1.
  • A cited study by Fujii and coauthors reported an association between the period of asbestos exposure and methylation at tumor suppressor genes, including RASSF1A, p16INK4a and RARβ.
  • Cited work attributed to Tsou and associates reported that methylation of the metallothionein genes MT1A and MT2A was significantly positively associated with asbestos burden.
  • A cited study by Nelson and colleagues reported that MSLN (mesothelin) promoter methylation was significantly higher in normal pleura than in mesothelioma tumor tissue.
• The authors' conclusion: The authors concluded that exposure timing, dose, sex and organ specificity must be considered before using these methylation changes as exposure biomarkers. They suggested that mixed exposure to toxicants and food-based reversers can alleviate or mask epigenetic toxicity in real life.
• Limitations the authors state:
  • The authors noted that the supplements and herbs sold for personal chemoprevention lack sufficient evidence.
  • The authors described the evidence on dietary epigenetic modulators as scattered reports.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker.

Related studies

• A Succinate Ether Derivative of Tocotrienol Enhances Dickkopf-1 Gene Expression through Epigenetic Alterations in Malignant Mesothelioma Cells — A. Sato, H. Ueno, et al. (2018)
• Diallylsulfide attenuates asbestos-induced genotoxicity — M. Lohani, S. Yadav, et al. (2003)
• Targeting epigenetic mediators of gene expression in thoracic malignancies — D.S. Schrump (2012)
• Genomic profiling of malignant peritoneal mesothelioma reveals recurrent alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X — N.M. Joseph, Y.Y. Chen, et al. (2017)
• Chemical interaction: enhancement and inhibition of clastogenicity — W.A. Anwar (1993)
• Environmental mutagens induced transversions but not transitions in regulatory region of mitochondrial DNA — M.A. Partridge, S.X. Huang, et al. (2009)

Browse return to medical research.