RELATIVE SUSCEPTIBILITIES OF XPA KNOCKOUT MICE AND THEIR HETEROZYGOUSAND WILD-TYPE LITTERMATES TO UVB-INDUCED SKIN-CANCER

Although xeroderma pigmentosum (XP) patients are rare, carriers of XP genes (heterozygotes) are much more common, Whether such carriers have an increased skin cancer risk is unknown. Recently developed mouse mo dels for XP have opened up the possibility of determining the skin can cer risk of heterozygotes relative to wild types, Therefore, the XPA k nockout trait has been crossed into hairless mice, and squamous cell c arcinomas of the skin have been induced by low daily WE exposures for 500 days in all three genotypes (-/-, +/-, and +/+), The carcinogenic response of the heterozygotes did not significantly differ from that o f their wild-tgpe littermates, Tumors in the XPA -/- animals appeared with a latency time that was decreased by a factor of 4.2, From this, we estimate that a functional XPA gene provides a ''protection factor' ' of 60 (95% confidence interval, 15-250) against UV carcinogenesis, w hich is greater protection than that against acute UV effects, such as erythema and edema (protection factor between 7 and 16), Deficient nu cleotide excision repair appears to have a more dramatic impact on ski n cancer susceptibility than on sensitivity to acute UV effects.