HIGH SUSCEPTIBILITY TO ULTRAVIOLET-INDUCED CARCINOGENESIS IN MICE LACKING XPC

COMPROMISE Of genetic information by mutation may result in the dysreg ulation of cellular growth control and subsequent tumour formation, Xe roderma pigmentosum (XP) is a rare autosomal disease characterized by hypersensitivity of the skin to sunlight and >1,000-fold increased ris k of skin cancers in sun-exposed parts of the body, Cell fusion studie s have revealed eight complementation groups In XP (A-G, and an XP-var iant form); group C is one of the most common forms of the disease(1). We have isolated a mouse homologue of the human gene for XP group C a nd generated XPC-deficient mice by using embryonic stem cell technolog y. Mice homozygous for the XPC mutant allele (xpc(m1)/xpc(m1)) are via ble and do not exhibit an increased susceptibility to spontaneous tumo ur generation at one year of age, However, xpc(m1)/xpc(m1) mice were f ound to be highly susceptible to ultraviolet-induced carcinogenesis co mpared with mice heterozygous for the mutant allele (xpc(m1)/+) and wi ld-type controls. Homozygous xpc(m1) mutant mice also display a spectr um of ultraviolet-exposure-related pathological skin and eye changes c onsistent with the human disease xeroderma pigmentosum group C.