The Human P53 Gene Mutated At Position 249 Per Se Is Not Sufficient to Immortalize Human Liver Cells

Schleger, Claudia; Becker, Roger; Oesch, Franz; Steinberg, Pablo

doi:10.1002/hep.510290305

Cited by 7 publications

(1 citation statement)

References 31 publications

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“…The 249 Ser mutant is more effective than other p53 mutants, including 143 Ala , 175 His , 248 Trp and 282 His , in inhibiting wildtype p53 transcriptional transactivating activity in human liver cells (Forrester et al, 1995). Schleger et al (1999) transfected a non-tumourigenic human liver epithelial cell line, HACL-1, which does not express detectable p53 protein, with the mutated 249 Ser sequence but this had no effect on the lifespan of the cells or their ability to grow in soft agar.…”

Section: The Contribution Of Mechanistic Understanding To Assessing the Carcinogenicity Of Aflatoxinmentioning

confidence: 99%

The toxicology of aflatoxins as a basis for public health decisions

Wild

Turner²

2002

Mutagenesis

418

302

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Aflatoxins have been extensively studied with respect to their mechanisms of toxicity. An understanding of metabolism, DNA adduct induction, mutagenicity and carcinogenicity has been paralleled by the development of biomarkers of aflatoxin exposure and biological effects (e.g. mutations) applied to human populations. The improvements in exposure assessment and their application in prospective epidemiological studies and the demonstration of a specific mutation in the TP53 gene in hepatocellular carcinomas from areas of high aflatoxin exposure have contributed significantly to the classification of aflatoxins as human carcinogens. In addition to establishing the carcinogenicity of aflatoxins in humans, understanding molecular mechanisms of action has provided the scientific rationale for prevention strategies, including primary and chemoprevention approaches. Overall, integrated, multidisciplinary research on aflatoxins has provided the platform on which to base decisions regarding acceptable exposures and priorities for interventions to reduce human risk in a public health context.

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Section: The Contribution Of Mechanistic Understanding To Assessing the Carcinogenicity Of Aflatoxinmentioning

confidence: 99%