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Toxicologic Pathology
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Journal Article

Relationship of DNA Adducts Derived from 2-Acetylaminofluorene to Cell Proliferation and the Induction of Rodent Liver and Bladder Tumors

Samuel M. Cohen

University of Nebraska Medical Center, Eppley Institute for Research in Cancer, Omaha, Nebraska 68198-3135

Leon B. Ellwein

National Eye Institute, Bethesda, Maryland 20892

Pharmacokinetic models have been developed to assist in extrapolating results from rodent bioassays. However, in numerous circumstances, it is necessary to combine such models with cellular response models to fully define interspecies and dose extrapolations. Interactions between pharmacokinetic target tissue end points (DNA adduct formation) and cellular proliferation in liver and urinary bladder carcinogenesis is illustrated with the results from the ED01 study involving 2-acetylaminofluorene administered to female mice. The interaction of genotoxic and cell proliferative effects are also illustrated in a co-carcinogenesis study with low doses of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide and high doses of sodium saccharin. The application of such interactions to humans is illustrated for the case of cigarette smoke-induced bladder cancer.

Key Words: Bladder carcinogenesis • liver carcinogenesis • risk assessment

Toxicologic Pathology, Vol. 23, No. 2, 136-142 (1995)
DOI: 10.1177/019262339502300206
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