Hypomethylation of DNA: a nongenotoxic mechanism involved in tumor promotion

Toxicology Letters
J L Counts, J I Goodman

Abstract

There is an abundant amount of information on the mechanisms of action of genotoxic chemicals that act as carcinogens and the role that mutations play in carcinogenesis. However, carcinogenesis is more than mutagenesis and many carcinogens are not mutagens. Thus, there is a need to consider nongenotoxic mechanisms that may be involved in carcinogenesis. In this paper, we review our working hypothesis that hypomethylation of DNA is an epigenetic, nongenotoxic mechanism that plays a role in tumor promotion by facilitating aberrant gene expression. The utility of employing experimental models that focus on relevant comparisons between sensitive and resistant strains of mice is emphasized. Additionally, aspects of DNA methylation in rodents and humans are compared and contrasted. We discuss hypomethylation of DNA as a secondary mechanism, that is expected to be threshold-exhibiting, and conclude by describing how this information may facilitate a rational approach towards risk assessment when dealing with nongenotoxic compounds that are carcinogenic in a bioassay.

References

Dec 24, 1992·Cell·J C ShenP A Jones
Nov 1, 1991·Journal of Toxicology and Environmental Health·R L Vorce, J I Goodman
Nov 1, 1991·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·J I GoodmanT R Fox
Aug 5, 1991·Journal of Molecular Biology·W Lee, E B Keller
Feb 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·A BuchmannM Schwarz
Jun 1, 1991·The American Journal of Physiology·D C Gruenert, A L Cozens
Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·B N Ames, L S Gold
Sep 15, 1989·Toxicology and Applied Pharmacology·R L Vorce, J I Goodman
Sep 1, 1988·The New England Journal of Medicine·B VogelsteinJ L Bos
Jan 26, 1989·Nature·R Holliday
Oct 9, 1987·Science·R Holliday
Jul 20, 1987·Journal of Molecular Biology·M Gardiner-Garden, M Frommer
Oct 1, 1985·Molecular and Cellular Biology·S PulcianiM Barbacid
Oct 11, 1983·Nucleic Acids Research·M A Gama-SosaM Ehrlich
Oct 23, 1981·Science·J H Weisburger, G M Williams
Jun 1, 1995·Regulatory Toxicology and Pharmacology : RTP·J L Counts, J I Goodman
Apr 21, 1995·Cell·P W LairdR Jaenisch
May 5, 1995·Science·R ParsonsB Vogelstein
May 1, 1995·Nature Genetics·S J ClarkM Frommer
Jan 1, 1995·Genetics·G H LeeN R Drinkwater
Feb 1, 1995·Regulatory Toxicology and Pharmacology : RTP·E E McConnell
Feb 1, 1995·Regulatory Toxicology and Pharmacology : RTP·J A Swenberg
Feb 1, 1995·Regulatory Toxicology and Pharmacology : RTP·S M Cohen
Jan 1, 1994·Human Molecular Genetics·P W Laird, R Jaenisch
Nov 1, 1994·Trends in Biochemical Sciences·G DaumU R Rapp
Dec 1, 1994·Molecular Carcinogenesis·J L Counts, J I Goodman
Jan 1, 1993·Proceedings of the Society for Experimental Biology and Medicine·Y P DraganH C Pitot
May 18, 1994·Journal of the National Cancer Institute·S Rainier, A P Feinberg
Nov 25, 1993·Nature·E LiR Jaenisch

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Citations

Aug 23, 2002·Seminars in Cancer Biology·John R Melki, Susan J Clark
Jul 22, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D AuneE De Stefani
Mar 5, 2004·Journal of the National Cancer Institute·Susanna C LarssonAlicja Wolk
Feb 22, 2008·Environmental Health Perspectives·Lamia Benbrahim-Tallaa, Michael P Waalkes
Mar 31, 1998·Environmental Health Perspectives·J I Goodman
Mar 1, 2009·Journal of Toxicologic Pathology·Robert R Maronpot
Jan 27, 2015·Toxicology and Applied Pharmacology·Robert M HarrisNikolas J Hodges
Aug 8, 2009·International Journal of Experimental Pathology·Femke HeindryckxHans Van Vlierberghe
Aug 11, 2004·Molecular Cancer·Anthony J BaisGabriel Kremmidiotis
Aug 7, 2003·Toxicology and Applied Pharmacology·Yoko HirabayashiTohru Inoue
Aug 7, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Moshe Szyf
Apr 3, 2001·American Journal of Epidemiology·R Z Stolzenberg-SolomonD Albanes
Mar 16, 2007·Carcinogenesis·Long LiMichael A Pereira
Sep 18, 2009·Harvard Men's Health Watch
Feb 24, 2001·Human & Experimental Toxicology·J E KlaunigY Xu
Jul 29, 1997·International Journal of Cancer. Journal International Du Cancer·J L CountsJ I Goodman
Feb 22, 2002·Journal of Biochemical and Molecular Toxicology·Rongrong GeMichael A Pereira
Apr 3, 2001·Journal of Biochemical and Molecular Toxicology·R GeM A Pereira
Jun 27, 1998·Biochemical and Biophysical Research Communications·Y TakahashiT Kamataki
Apr 1, 1997·Mutation Research·S Cerda, S A Weitzman
Aug 6, 2002·Molecular and Cellular Endocrinology·Frank J Gonzalez

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