TY - JOUR
T1 - Studies of in vivo mutations in rpsL transgene in UVB-irradiated epidermis of XPA-deficient mice
AU - Murai, Hiroaki
AU - Takeuchi, Seiji
AU - Nakatsu, Yoshimichi
AU - Ichikawa, Minoru
AU - Yoshino, Masafumi
AU - Gondo, Yoichi
AU - Katsuki, Motoya
AU - Tanaka, Kiyoji
N1 - Funding Information:
We thank Dr. Hisaji Maki for providing supF plasmid pFSE101, and Miss Tan Bee Tee for reading the manuscript. This work has been supported by grants from the Ministry of Education, Science, Sports and Culture of Japan [Grant-in-Aid for Scientific Research (A) (11307056), Grant-in-Aid for Scientific Research on Priority Areas (08280101)], by Health Science Research Grants for Research on Human Genome and Gene Therapy from the Ministry of Health and Welfare of Japan [H10-Genome-021], and by CREST, JST (Japan Science and Technology).
PY - 2000/5/30
Y1 - 2000/5/30
N2 - 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.
AB - 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.
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U2 - 10.1016/S0027-5107(00)00024-5
DO - 10.1016/S0027-5107(00)00024-5
M3 - Article
C2 - 10838142
AN - SCOPUS:0034732984
SN - 0027-5107
VL - 450
SP - 181
EP - 192
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -
