DNA methylation, heterochromatin and epigenetic carcinogens.
This paper will explore emerging concepts related to alternative carcinogenic mechanisms of 'non-mutagenic,' and hence epigenetic, carcinogens that may heritably alter DNA methylation without changing the underlying DNA sequence. In this review, we will touch on the basic concepts of DNA methylation, and will elaborate in greater detail on related topics including chromatin condensation, and heterochromatin spreading that is well known to induce gene silencing by position effect variegation in Drosophila and other species. Data from our model transgenic G12 cell system will be presented to support our hypothesis that certain carcinogens, such as nickel, may be carcinogenic not primarily because of their overt mutability, but rather as the result of their ability to promote DNA hypermethylation of important cancer-related genes. We will conclude with a discussion of the broader relevance of our findings and its application to other so-called 'epigenetic' carcinogens.
Klein
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CB
Nelson Institute of Environmental Medicine, New York University Medical Center, NY 10016, USA.
Costa
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M
D000818:Animals; D005075:Biological Evolution; D002273:Carcinogens / Q000145:classification / Q000633:toxicity*; D002843:Chromatin / Q000187:drug effects* / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects*; D004054:Diethylstilbestrol / Q000633:toxicity; D005544:Forecasting; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics; D009532:Nickel / Q000633:toxicity; D010084:Oxidation-Reduction; D016615:Telomere / Q000235:genetics
D002273:Carcinogens; D002843:Chromatin; D009153:Mutagens; D004054:Diethylstilbestrol; D009532:Nickel