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Epigenetic mechanisms of chemical carcinogenesis

Division of Toxicology, Department of Pharmacology and Toxicology, Indiana University, Indianapolis, Indiana, USA; Indiana University School of Medicine, 635 Barnhill Drive, MS-1021 Indianapolis, Indiana 46202-5120, USA

L M Kamendulis

Yong Xu

Division of Toxicology, Department of Pharmacology and Toxicology, Indiana University, Indianapolis, Indiana, USA

Chemically induced cancer is a multi-step process involving damage to the genome initially followed by clonal expansion of the DNA damaged cell eventually leading to a neoplasm. Chemical carcinogens have been shown to impact at all of the stages of the tumorigenesis process. It has become apparent that chemical and physical agents that induce cancer may do so through several different cellular and molecular mechanisms. Epigenetic (nongenotoxic) chemical carcinogens are those agents that function to induce tumor formation by mechanisms exclusive of direct modification or damage to DNA. These agents appear to modulate cell growth and cell death and exhibit dose response relationships between exposure and tumor formation. The exact and/or exclusive mechanisms by which these agents function have not been established, however, changes in cell growth regulation and gene expression are important to tumor formation. This review focuses on several potential mechanisms and cellular processes that may be involved in nongenotoxic chemical carcinogenesis.

Key Words: epigenetic • carcinogenesis • cell proliferation • gene expression

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