Mouse models for generating P53 gene mutation spectra.
The p53 tumor suppressor gene lends itself to mutation spectra analysis, because the frequency of point mutations in human tumors is high, the locations of inactivating tumor mutations are numerous and dispersed, and all possible base substitutions are observed in human cancer. P53 tumor mutations induced experimentally in mice exposed to carcinogens have been described, but have not yet contributed significantly to our understanding of mutagenic mechanisms or of the origins of mutations in human cancers. Recently, gene-targeting technology has allowed development of a new mouse model, which explores experimentally the endogenous and environmental factors that may contribute to neoplastic disease in humans.
Department of Genetic Alterations in Carcinogenesis, German Cancer Research Center, Dept C0700, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Boris
B
Zielinski
Zhipei
Z
Liu
Monica
M
Hollstein
Manfred
M
Hergenhahn
Jun-Li
JL
Luo
D000818:Animals; D015197:Carcinogenicity Tests; D004195:Disease Models, Animal; D004781:Environmental Exposure / Q000009:adverse effects*; D018390:Gene Targeting / Q000379:methods; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009369:Neoplasms / Q000209:etiology / Q000235:genetics; D017354:Point Mutation; D015262:Xenobiotics / Q000633:toxicity
D015262:Xenobiotics