Apoptosis and cancer risk assessment.
Apoptosis is one form of physiological or active cell death. The balance between cell proliferation and cell death or apoptosis not only effects organ growth but also has a profound impact on the net increase and growth of initiated cells and preneoplastic and tumor cell populations. With respect to cancer development apoptosis is becoming widely recognized as being an innate tissue defense against carcinogens by inhibiting survival and controlling growth of precancerous cell populations and tumors at different stages of carcinogenesis. Experimental data on cell birth and cell death rates help identify the mode of action of a chemical and can be incorporated into biologically based cancer models. This article describes the quantitation and regulation of apoptosis in rodent liver and how loss of regulation can have a role in hepatocarcinogenesis. A biologically-based mouse liver cancer model is presented and utilized to describe how treatment related growth effects affect the process of carcinogenesis. Advantages and limitations of biologically based cancer models in cancer research and risk assessment are discussed.
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709-2137, USA. goldsworthy@ciit.org
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Goldsworthy
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Conolly
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Fransson-Steen
D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000633:toxicity; D002455:Cell Division; D008113:Liver Neoplasms / Q000473:pathology*; D051379:Mice; D018570:Risk Assessment
D002273:Carcinogens