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个人简介
Dr. Pitot carried out ground-breaking research in the molecular biology of multistage carcinogenesis, authoring or coauthoring over 500 scientific papers. His pioneering studies on the regulation and quantitation of defective gene expression in the stages of initiation, promotion, and progression of liver cancer have provided fundamental insights into multistage carcinogenesis. His early studies demonstrated that the environmental regulation of gene expression in primary and transplanted hepatocellular carcinomas was defective and significantly different from that in normal and host liver (Annu. Rev. Biochem., 35: 335-368, 1966). These observations led to the development of methods for the identification and quantitation of preneoplastic lesions in the livers of carcinogen-treated rodents (Nature, 271: 456-458, 1978; Cancer Res., 42: 465-472, 1982). Analysis of the growth and development of these precursor lesions has made it possible to discriminate between the initiating and promoting activities of environmental chemicals or drugs (J. Toxicol. Environ. Health, 16: 389-402, 1985) and to compare directly their biological potencies (Environ. Health Persp., 76: 49-56, 1987). Such studies have shown that the dose-response for promoting agents is non-linear and that the biological activities of promoting agents vary over eight orders of magnitude. These discoveries have important implications for our ability to identify potential carcinogens and to evaluate the risk they pose for the human population. In parallel Dr. Pitot and his colleagues made seminal contributions to isolating and maintaining strains of hepatocytes in culture (J. Cell. Physiol., 147: 495-504, 1991; In Vitro Cell. Dev. Biol. 31: 867-870, 1995). These studies provide the basis for characterizing those cells that metabolize the bulk of the carcinogenic compounds to which we are exposed.
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