Allelic losses in mouse skin tumors induced by gamma-irradiation of p53 heterozygotes.
Skin tumors were induced by gamma-irradiation in F(1) mice between C3H/He or BALB/c and MSM carrying a p53-deficient allele. The incidence was 39.1% (34/87) in p53(KO/+) mice of the C3H/MSM genetic background and 14.3% (19/133) in those of the BALB/MSM background. Interestingly, most of the tumors (82%) lost the wild-type p53 allele and no skin tumor was found in p53(+ / +) F(1) mice. This suggests a requirement of p53 loss for the skin cancer development. Genome scan localized a chromosomal locus showing frequent allelic losses near D12Mit2, which may harbor a tumor suppressor gene. In addition, 23 loci distributed on 13 chromosomes exhibited allelic losses at frequencies of more than 20%. The genome-wide occurrence of allelic losses suggests that genomic instability of the skin tumors may be implicated in radiation-induced carcinogenesis. The present study is the first to report a mouse model system useful for the analysis of radiation induction of skin cancer in man.
D000483:Alleles; D000818:Animals; D005720:Gamma Rays; D016158:Genes, p53; D006579:Heterozygote; D019656:Loss of Heterozygosity; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*