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Epigenetics and epimutagens: some new perspectives on cancer, germ line effects and endocrine disrupters
1School of Microbiology, La Trobe University, Bundoora, Victoria 3083, Australia. micdgm@lure.latrobe.edu.au
Abstract:
It is known that a variety of chemicals, including certain base analogues and reactive oxygen species, can alter the phenotypes of mammalian cells epigenetically, i.e., without changing their DNA sequence information in any way. The implications of such findings are not trivial, but do not seem to have been the focus of a great deal of attention amongst mutation researchers to date. In part this may be a reflection of the confused state of terminology in the chemical carcinogenesis research area and in part may signal a reluctance on the part of many of us to come to terms with the idea of heritable non-sequence changes to DNA molecules. In this review, some of the most obvious outcomes of spontaneous and induced epimutagenic change for human carcinogenesis and germ line inheritance are discussed, and an attempt is made to place the so-called endocrine disrupters in a context in which their modes of action may be more readily analysed and integrated into the broader chemical hazard framework.
Insights
Chemicals can epigenetically alter cell phenotypes without changing DNA sequence. This review discusses epimutations in human carcinogenesis and inheritance, and endocrine disruptors within chemical hazard assessment.
Area of Science:
- Epigenetics and Chemical Carcinogenesis
- Genomic Instability and Heritable Changes
Background:
- Mammalian cell phenotypes can be altered epigenetically by chemicals like base analogues and reactive oxygen species.
- Epigenetic modifications, which do not alter DNA sequence, have significant implications but are understudied in mutation research.
- Confusion in terminology and reluctance to accept heritable non-sequence DNA changes may hinder research.
Purpose of the Study:
- To review the outcomes of epimutagenic changes in human carcinogenesis and germline inheritance.
- To contextualize endocrine disruptors within a broader chemical hazard framework for mode of action analysis.
Main Methods:
- Review of existing literature on epimutations and chemical carcinogenesis.
- Analysis of spontaneous and induced epimutagenic changes.
- Discussion of endocrine disruptors' mechanisms of action.
Main Results:
- Epimutagenic changes can impact human carcinogenesis and germline inheritance.
- Endocrine disruptors can be analyzed within a broader chemical hazard framework.
Conclusions:
- Epigenetic alterations represent a significant, yet underexplored, area in mutation research.
- Understanding epimutations is crucial for assessing chemical hazards, including endocrine disruptors, and their impact on health and inheritance.