Tumor development in the skin may be a multistep process where multiple genetic 
alterations occur successively. The p53 gene is involved in genome stability and 
thus is referred to as "the guardian of the genome." To better understand the 
antigenotoxic effects of p53 in ultraviolet light B (UVB)-induced mutagenesis, 
mutations were measured in the epidermis of UVB-irradiated p53(+/+) and p53(-/-) 
gpt delta mice. In the mouse model, point mutations and deletions are separately 
identified by the gpt and Spi(-) assays, respectively. The mice were exposed to 
UVB at single doses of 0.5, 1.0, or 2.0 kJ/m(2) . The mutant frequencies (MFs) 
were determined 4 weeks after the irradiation. All doses of UVB irradiation 
enhanced gpt MFs by about 10 times than that of unirradiated mice. There were no 
significant differences in gpt MFs and the mutation spectra between p53(+/+) and 
p53(-/-) mice. The predominant mutations induced by UVB irradiation were G:C to 
A:T transitions at dipyrimidines. In contrast, in unirradiated p53(-/-) mice, 
the frequencies of Spi(-) large deletions of more than 1 kb and complex-type 
deletions with rearrangements were significantly higher than those of the Spi(-) 
large deletions in p53(+/+) counterparts. The specific Spi(-) mutation frequency 
of more than 1 kb deletions and complex types increased in a dose-dependent 
manner in the p53(+/+) mice. However, no increase of such large deletions was 
observed in irradiated p53(-/-) mice. These results suggest that the 
antigenotoxic effects of p53 may be specific to deletions and complex-type 
mutations induced by double-strand breaks in DNA.