Analysis of mutation induced in UV-irradiated skin

• Project/Area Number: 11680541
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 環境影響評価(含放射線生物学)
• Research Institution: Tohoku University
• Principal Investigator: IKEHATA Hironobu Graduate School of Medicine, Tohoku University, Research Associate, 大学院・医学系研究科, 助手 (90250737)
• Project Period (FY): 1999 – 2000
• Project Status: Completed (Fiscal Year 2000)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: Mutation / UV / Skin / Transgenic mouse / Skin cancer

Research Abstract

It is important to develop an efficient and simple method for evaluation of the frequency of sunlight-induced mutation in mammalian skin because the recent increase of the ultraviolet light (UV) component of sunlight has caused significant induction of human skin carcinoma. Utilizing a bacterial lacZ gene-introduced transgenic mouse Muta^<TM>, which has been widely used for in vivo assay of induced mutations in an animal body exposed to various mutagens, we studied the induced mutations in mouse dorsal skin irradiated with three kinds of UV sources ; UVB, UVA and solar UV.We showed each source could increase efficiently and dose-dependently the frequency of the lacZ mutants in skin genome. DNA sequence changes in the lacZ gene of the mutants recovered from the irradiated skin were analyzed, and the UV-specific mutations of G : C to A : T at dipyrimidine sites were found in more than 80% of the mutant clones irrespective of the UV sources. We also detected CC to TT tandem base substitutions, which has been considered as the most representative mutation signifying UV exposure, with all UV sources. These results indicate that the animal system introduced here will be useful for the quantitative risk evaluation of skin cancer with the sunlight exposure of human skin.

Research Products

• [Publications] Horiguchi Mieko, et al.: "UVB-Induced gpt Mutations in the Skin of gpt delta Transgenic Mice."Environmental and Molecular Mutagenesis. 34・2-3. 72-79 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ono Tetsuya, et al.: "Age-associated increase of spontaneous mutant frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse."Mutation Research. 447・2. 165-177 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ikehata Hironobu, et al.: "Distribution of Spontaneous CpG-Associated G : C→A : T Mutations in the lacZ gene of Muta^<TM> Mice : Effects of CpG Methylation, the Sequence Context of CpG Sites, and Severity of Mutations on the Activity of the lacZ Gene Product."Environmental and Molecular Mutagenesis. 36・4. 301-311 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Horiguchi Mieko, et al.: "UVB-Induced gpt Mutations in the Skin of gpt delta Transgenic Mice."Environmental and Molecular Mutagenesis. 34(2-3). 72-79 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ono Tetsuya, et al.: "Age-associated increase of spontaneous mutant frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse."Mutation Research. 447(2). 165-177 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ikehata Hironobu, et al.: "Distribution of Spontaneous CpG-Associated G : C→A : T Mutations in the lacZ gene of Muta^<TM> Mice : Effects of CpG Methylation, the Sequence Context of CpG Sites, and Severity of Mutations on the Activity of the lacZ Gene Product."Environmental and Molecular Mutagenesis. 36(4). 301-311 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ikehata Hironobu, et al.: "Distribution of Spontaneous CpG-Associated G : C→A : T Mutations in the lacZ gene of Muta^<TM> Mice : Effects of CpG Methylation, the Sequence Context of CpG Sites, and Severity of Mutations on the Activity of the lacZ Gene Product"Environmental and Molecular Mutagenesis. 36・4. 301-311 (2000)
• [Publications] Horiguchi M.et al.: "UVB-induced gpt mutations in the skin of gpt delta transgenic mice"Environmental and Molecular Mutagenesis. 34(2-3). 72-79 (1999)
• [Publications] Tetsuya Ono et al.: "Age-associated increase of spontaneous mutant frequency and molecular nature of mutation in newborn and old lacZ-transgenic mouse"Mutation Research. (in press). (2000)