HIGH-INCIDENCE OF ULTRAVIOLET-B-INDUCED OR CHEMICAL-CARCINOGEN-INDUCED SKIN TUMORS IN MICE LACKING THE XERODERMA-PIGMENTOSUM GROUP-A GENE

XERODERMA pigmentosum (XP) is an autosomal recessive disorder characte rized by a high frequency of skin cancer on sun-exposed areas, and neu rological complications, XP has a defect in the early step(s) of nucle otide-excision repair (NER) and consists of eight different genetic co mplementation groups (groups A-G and a variant)(1). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physic al abnormalities nor pathological alterations, but were defective in N ER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[ a]anthracene-induced skin carcinogenesis. These findings provide is vi vo evidence that the XPA protein protects mice from carcinogenesis ini tiated by ultraviolet or chemical carcinogen, The XPA-deficient mice m ay provide a good in vivo model to study the high incidence of skin ca rcinogenesis in group A XP patients.