We have established xeroderma pigmentosum group A (XPA) gene-knockout mice with nucleotide excision repair (NER) deficiency, which rapidly developed skin tumors when exposed to a low dose of chronic UV like XP-A patients, confirming that the NER process plays an important role in preventing UVB-induced skin cancer. To examine the in vivo mutation in the UVB-irradiated epidermis, we established XPA (-/-), (+/-) and (+/+) mice carrying the Escherichia coli rpsL transgene with which the mutation frequencies and spectra in the UVB-irradiated epidermal tissue can be examined conveniently. The XPA (-/-) mice showed a higher frequency of UVB-induced mutation in the rpsL transgene with a low dose (150 J/m2) of UVB-irradiation than the XPA (+/-) and (+/+) mice, while, at a high dose (900 J/m2) they showed almost the same frequency of mutation as the XPA (+/-) and (+/+) mice, probably because of cell death in the epidermis of the XPA (-/-) mice. However, CC→TT tandem transition, a hallmark of UV-induced mutation, was detected at higher frequency in the XPA (-/-) mice than the XPA (+/-) and (+/+) mice at both doses of UVB. This rpsL/XPA mouse system will be useful for further analyzing the role of NER in the mutagenesis and carcinogenesis induced by various carcinogens. Copyright (C) 2000 Elsevier Science B.V.
|Number of pages||12|
|Journal||Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis|
|Publication status||Published - May 30 2000|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Health, Toxicology and Mutagenesis