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

Hiroaki Murai, Seiji Takeuchi, Yoshimichi Nakatsu, Minoru Ichikawa, Masafumi Yoshino, Yoichi Gondo, Motoya Katsuki, Kiyoji Tanaka

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)181-192
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume450
Issue number1-2
DOIs
Publication statusPublished - May 30 2000
Externally publishedYes

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Xeroderma Pigmentosum
Transgenes
Epidermis
Mutation
DNA Repair
Mutation Rate
Gene Knockout Techniques
Skin Neoplasms
Knockout Mice
Mutagenesis
Carcinogens
Carcinogenesis
Cell Death
Escherichia coli
Skin

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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Studies of in vivo mutations in rpsL transgene in UVB-irradiated epidermis of XPA-deficient mice. / Murai, Hiroaki; Takeuchi, Seiji; Nakatsu, Yoshimichi; Ichikawa, Minoru; Yoshino, Masafumi; Gondo, Yoichi; Katsuki, Motoya; Tanaka, Kiyoji.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 450, No. 1-2, 30.05.2000, p. 181-192.

Research output: Contribution to journalArticle

Murai, Hiroaki ; Takeuchi, Seiji ; Nakatsu, Yoshimichi ; Ichikawa, Minoru ; Yoshino, Masafumi ; Gondo, Yoichi ; Katsuki, Motoya ; Tanaka, Kiyoji. / Studies of in vivo mutations in rpsL transgene in UVB-irradiated epidermis of XPA-deficient mice. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2000 ; Vol. 450, No. 1-2. pp. 181-192.
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