Studies of in vivo mutations in rpsL transgene in UVB-irradiated epidermis of XPA-deficient mice.
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/m(2)) of UVB-irradiation than the XPA (+/-) and (+/+) mice, while, at a high dose (900 J/m(2)) 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.
Murai
H
H
Division of Cellular Genetics, Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamadaoka, Osaka 565-0871, Suita, Japan.
Takeuchi
S
S
Nakatsu
Y
Y
Ichikawa
M
M
Yoshino
M
M
Gondo
Y
Y
Katsuki
M
M
Tanaka
K
K
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D005260:Female; D005798:Genes, Bacterial; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000091243:Ribosomal Protein S9; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism; D051760:Xeroderma Pigmentosum Group A Protein
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D016601:RNA-Binding Proteins; D000091243:Ribosomal Protein S9; C000717190:RpsI protein, E coli; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; D004247:DNA