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International Journal of Toxicology
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Cancer Risk Assessment Strategies Based on Mechanisms of Action

John H. Weisburger

American Health Foundation 1 Dana Road Valhalla, NY 10595–1599

The induction of cancer by chemicals is a complex process that involves a series of steps, proceeding from the neoplastic conversion of a normal cell, i.e., the discrete mechanistically distinct initiation of a neoplastic cell, through the steps involving promotion, development, and progression. Chemicals can act in each of these stages as initiators, cocarcinogens, promoters, or inhibitors of carcinogenesis. Chemicals must be classified as operating by genotoxic or epigenetic mechanisms. Appropriate short-term in vitro tests used as a battery can be applied to detect such properties. These abbreviated and economic tests have good qualitative decision-making potential, since they are based on mechanisms of action. Advances in molecular biology may provide additional tests to detect cancer risk. Quantitative data available from in vivo dose-response studies demonstrate that carcinogenic effects are dose dependent, and, therefore, a threshold or no-effect level probably exists that is low for potent carcinogens, especially genotoxins, and high for weaker ones, particularly epigenetic agents. A set of mechanism-oriented data must be acquired systematically to serve as basis for realistic and effective risk assessment and management.

International Journal of Toxicology, Vol. 7, No. 4, 417-425 (1988)
DOI: 10.3109/10915818809019511
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