Allelic Losses in Mouse Skin Tumors Induced by γ-Irradiation of p53 Heterozygotes

Skin tumors were induced by γ-irradiation in F₁ 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 (+/+) F₁ 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.