Studies of in vivo mutations in rpsL transgene in UVB-irradiated epidermisof XPA-deficient mice

We have established xeroderma pigmentosum group A (XPA) gene-knockout mice with nucleotide excision repair (NER) deficiency, which rapidly developed s kin tumors when exposed to a low dose of chronic UV like XP-A patients, con firming that the NER process plays an important role in preventing UVB-indu ced skin cancer. To examine the in vivo mutation in the UVB-irradiated epid ermis, we established XPA(- / -), (+ / -) and(+ / +) mice carrying the Esch erichia coil rpsL transgene with which the mutation frequencies and spectra in the UVB-irradiated epidermal tissue can be examined conveniently. The X PA (- / -) mice showed a higher frequency of UVB-induced mutation in the rp sL transgene with a low dose (150 J/m(2)) of UVB-irradiation than the XPA ( + / -) and (+ / -) mice, while, at a high dose (900 J/m(2)) they showed alm ost the same frequency of mutation as the XPA (+ / -) and (+ / +) mice, pro bably because of cell death in the epidermis of the XPA (- / -) mice. Howev er, CC --> TT tandem transition, a hallmark of W-induced mutation, was dete cted at higher frequency in the XPA (- / -) mice than the XPA (+ / -) and ( + / +) mice at both doses of UVB. This rpsL / XPA mouse system will be usef ul for further analyzing the role of NER in the mutagenesis and carcinogene sis induced by various carcinogens. (C) 2000 Elsevier Science B.V. All righ ts reserved.