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Molecular Epidemiology of Genetic Damage and its Repair

Research Project

Project/Area Number 06045021
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionUniversity-to-University Cooperative Research
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

TAKEBE Hiraku  Faculty of Medicine, Kyoto University, 医学研究科, 教授 (10028318)

Co-Investigator(Kenkyū-buntansha) COLE Jane  MRC Cell Mutation Unit, University of Sussex, 細胞変異研究所, 助教授
CARR Antony M  MRC Cell Mutation Unit, University of Sussex, 細胞変異研究所, 助教授
LEHMANN Alan  MRC Cell Mutation Unit, University of Sussex, 細胞変異研究所, 教授
BRIDGES Brian A  MRC Cell Mutation Unit, University of Sussex, 細胞変異研究所, 教授
TATSUMI Junko  Faculty of Medicine, Kyoto University, 医学研究科, 助手 (80128222)
MIYAKOSHI Junji  Faculty of Medicine, Kyoto University, 医学研究科, 助教授 (70121572)
YAGI Takashi  Faculty of Medicine, Kyoto University, 医学研究科, 助教授 (80182301)
BRIDGES Bria  サセックス大学, 細胞変異研究所, 教授
JEGGO Penny  サセックス大学, 細胞変異研究所, 助教授
COLE J.  サセックス大学, 細胞変異研究所, 助教授
塚田 俊彦  京都大学, 医学部, 助手 (10207334)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1994: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsepidemiology / DNA repair / xeroderma pigmentosum / leukemia / radiation / gene / 色素乾皮症 / 突然変異 / 発がん / 分裂酵母 / 紫外線 / 修復 / 分子疫学 / 皮膚がん
Research Abstract

Molecular epidemiology is a new area of medical science to find the causes and mechanisms of diseases assoicaited with damage in DNA.Radiation causes damage in DNA leading to mutation and cancer. There are human subjects sensitive to radiations. This study intends to analyze changes in DNA in the cancer patients or their cells in relation to DNA repair. Patients with hereditary diseases associated with DNA repair deficiency are generally sensitive to radiations and other environmental agents. Detailed analysis of the patients with xeroderma pigmentosum (XP) in Japan and UK revealed that the sites of mutations responsible for XP are different between the patients in Japan and those in UK.The sites were related to the clinical symptom of the patients. Most of the XP group A patients in Japan had a common mutatio at the end of intron 3 of XPA gene, while XPA patients in UK had mutations in other sites which may not be important for the function of the gene.
High incidence of childhood leukemia in children of the workers at some of nuclear factories has been a very controversial issue in UK during last several years. Prof.B.A.Bridges of University of Sussex, a member of this study group, is chairman of the committee to investigate the case. The committee published a detailed final report in 1996, and Prof. Bridges visited Kyoto University to give a lecture and have discussion on this matter. The leukemia cases were not attributed to the radiations, but other causes were not detected. Molecular epidemiological studies on each case of leukemia may provide clues to the real causes of the disease in future, according to Prof. Bridges, as certain agents are known to cause specific changes in DNA.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Toshihiko Tsukada: "Functional analysis of the cell-specific enhancer in the human proopiomelanocortin gene by -galactosidase." DNA Cell Biol.13. 755-762 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Bokshil Shung: "X-ray-induced transcriptional activation of c-mos and XRCCI genes in ataxia telangiectasia cells." Mutat.Res.307. 43-51 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Junji Miyakoshi: "A newly designed experimental system for exposure of mammlian cells to extremely low frequency magnetic fields." J.Radiat.Res.35. 26-34 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takashi Yagi: "Similarity in the molecular profile of mutations induced by UV light in shuttle vector plasmids." Mutagenesis. 9. 73-73 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Mayumi Sato: "Far less frequent mutation in ras genes than in p53 gene in skin tumors fo xeroderma pigmentosum patients." Mol.Carcinog.11. 98-105 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Chikako Nishigori: "Mutations in ras genes in cells cultured from mouse skin tumors induced by ultraviolet irradiation." Proc.Natl.Acad.Sci.U.S.A.91. 7189-7193 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yasuhiro Matsumura: "High prevalence of mutations in the p53 gene in poorly differntiated squamous cell carcinomas in xeroderma pigmentosum patients." J.Invest.Dermatol.105. 399-401 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toshihiko Tsukada: "Vasoactive intestinal peptide gene expression in the rat pheochromocytoma cell line PC12." Mol.Cell.Endocrinol.107. 231-239 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tomonari Matsuda: "Molecular analysis of mutations induced by 2-chloroacetaldehyde,the ultimate carcinogenic form or vinyl chloride,in human cells using shuttle vectors." Carcinogenesis. 16. 2389-2394 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Junji Miyakoshi: "Changes in radiation sensitivity of human osteosarcoma cells after p53 introduction." Jpn.J.Cancer Res.86. 711-713 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nobuyuki Yamagishi: "Modification of the radiosensitivity of human cells to which simian virus 40 T-antigen was transfected." J.Radiat.Res.36. 239-247 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shuji Ohtsu: "Enhancement of β-galactosidase gene expression in rat pheochromocytoma cells by exposure to extremely low frequency magnetic fields." Biochem.Biophys.Res.Commun.212. 104-109 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yanjun Lu: "Sites and types of UV-induced mutations leading to inactivation of the growth-arresting activity in p21(sdil/cipl/wafl)cDNA." Carcinogenesis. 17. 2343-2345 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yasuhiro Matsumura: "Characterization of p53 gene mutations in basal-cell carcinomas:comparison between sun-exposed and less-exposed skin areas." Int.J.Cancer. 65. 778-780 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Junji Miyakoshi: "Exposure to magnetic field(5mT at 60 Hz)does not affect cell growth and c-myc gene expression." J.Radiat.Res.37. 185-191 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tomonari Matsuda: "Detection and quantification of DNA strand breaks in human cells induced by contaminants in Japanese tap waters." Wat.Sci.Tech.33. 297-304 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Junji Miyakoshi: "Increased radiosensitivity of p16 gene-deleted human glioma cells after transfection with wild-type p16 gene." Jpn.J.Cancer Res.88. 34-38 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Junji Miyakoshi: "Mutation induction by high-density,50 Hz magnetic field in human MeWo cells exposed in the DNA synthesis phase." Int.J.Radiat.Biol.71. 75-79 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiraku Takebe: "DNA Repair Mechanisms:Impact on Human Diseases and Cancer,Chapter 11(Edited by J.-H.Vos)" R.G.Landes Company, 239-246 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsukada, T., Nakai, Y., Fukushima, M., Usui, T., Imura, H.and Takebe, H.: "Functional analysis of the cell-specific enhancer in human proopiomelanocortin gene by beta-galactosidase" DNA and Cell Biology. 13. 755-762 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shung, B., Miyakoshi, J.and Takebe, H.: "X-ray-induced transcriptional activation of c-myc and XRCCl genes in ataxia telangiectasia" Mutation Research. 307. 43-51 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyakoshi, J., Ohtsu, S., Tatsumi-Miyakima, J.and Takebe, H.: "A newly designed experimental system for exposure of mammalian cells to extremely low frequncy magnetic fields" Journal of Radiation Research. 35. 26-34 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yagi, T., Sato, M., Nishigori, C.and Takebe H.: "Similarity in the molecular profile of mutations induced by UV light in shuttle vector plasmids propagated in mouse and human cells" Mutagenesis. 9. 73-77 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato, M., Nishigori, C., Lu, Y., Zghal, M., Yagi, T.and Takebe, H.: "Far less frequent mutations in ras genes than in the p53 gene in skin tumors of xeroderma pigmentosum patients." Molecular Carcinogenesis. 11. 98-105 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishigori, C., Wang, S., Sato, M., Miyakoshi, J., Tsukada, T.Yagi, T., Takebe, H.: "Mutations in ras genes in cells cultured form mouse skin tumors induced by ultraviolet irradiation" Proceedings of National Academy of Science, USA. 91. 7189-7193 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsumura, Y., Sato, M., Nishigori, C., Zghal, M., Yagi, T., Imanura, S.and Takebe, H.: "High prevalence of mutations in the p53 gene in poorly differentiated squamous cell carcinomas in xeroderma pigmentosum patients" Journal of Investigative Dermatology. 105. 399-401 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsukada, T., Fukushima, M., Takebe, H.and Nakai Y.: "Vasoactive intestinal peptide gene expression in the rat pheochromocytoma cell line PC12" Molecular and Celluar Endocrinology. 107. 231-239 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuda, T., Yagi, T., Kawanishi, M., Matsui, S.and Takebe, H.: "Molecular analysis of mutations induced by 2-chloro-acetaldehyde, the ultimate carcinogenic form of vinyl chloride, in human cells using shuttle vectors" Carcinogenesis. 16. 2389-2394 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyakoshi, J., Yamagishi, N., Ohtsu, S.and Takebe, H.: "Changes in radiation sensitivity of human osteosarcoma cells aftor p53 introduction" Japanese Journal of Cancer Research. 86. 711-713 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamagishi, N., Miyakoshi, J., Ohtsu, S., Day, III,R.S.and Takebe, H.: "Modification of the radiosensitivity of human cells to which simial virus 40 T-antigen was transfected" Journal of Radiation Research. 36. 239-247 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Othsu, S., Miyakoshi, J., Tsukada, T., Hiraoka, M., Abe, M.and Takebe, H.: "Enhancement of beta-galactosidase gene expression in rat pheochromocytoma cells by exposure to extremely low frequency magnetic fields" Biochemical Biophysical Research Communications. 212. 104-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Lu, Y., Yamagishi, N., Miyakoshi, J., Noda, A., Yagi, T.and Takebe, H.: "Sites and types of UV-induced mutations leading to inactivation of the growth arresting activity in p21 (sdil/cipl/wafl) cDNA" Carcinogenesis. 17. 2343-2345 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsumura, Y., Nishigori, C., Yagi, T., Imamura, S.and Takebe, H.: "Characterization of p53 gene mutations in basal-cell carcinomas : comparison between sun-exposed and less-exposed skin areas" International Journal of Cancer. 65. 775-780 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyakoshi, J., Ohtsu, S., Shibata, T.and Takebe, H.: "Exposure to magnetic field (5mT at 60Hz) does not affect cell growth and c-myc gene expression" Journal of Radiation Research. 37. 185-191 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsuda, T., Yagi, T., Takebe, H.and Matsui S.: "Detection and quatification of DNA strand breaks in human cells induced by contaminants in Japanese tap waters" Water Science and Technology. 33. 297-304 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyakoshi, J., Kitagawa, K., Yamagishi, N., Ohtsu, S., Day, R.S.and Takebe, H.: "Increased radiosensitivity of p16 gene-deleted human glioma cells after transfection with wild-type p16 gene" Japanese Journal of Cancer Research. 88. 34-38 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyakoshi, J., Kitagawa, K.and Takebe, H.: "Mutation induction by high-density, 50-Hz magnetic fields in human MeWo cells exposed in the DNA synthesis phase" International Journal of Radiation Biology. 71. 75-79 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nishigori, C., Moriwaki, S., Takebe, H., Tanaka, T.and Imamura, S.: "Gene alterations and clinical characteristics of xeroderma pigmentosum group A patients in Japan" Archives of Dermatology. 130. 191-197 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kushunoki, Y., Hayashi, T., Hirai, Y., Kushiro, J., Tatsumi, K., Kurihara, T., Zghal, M., Kamoun, M.R., Takebe, H., Jeffreys, A., Nakamura, N.and Akiyama, M.: "Increased rate of spontaneous mitotic recombination in T lymphocytes from a Bloom's syndrome patient using a flow-cytometric assay at HLA-A locus" Japanese Journal of Cancer Research. 85. 610-618 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyakoshi, J., Yamagishi, N., Ohtsu, S., Mohri, K.and Takebe, H.: "Increase in hypoxanthine-guanine phosphoribosyl transferase gene mutations by exposure to high-density 50Hz magnetic fields" Mutation Research. 349. 109-114 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takebe, H., Nishigori, C., Sato, M., Matsumura, Y.and Yagi, T.: Chapter 11 (Edited by J.-H.Vos) R.G.Landes Company. DNA Repair Mechanisms : Impact on Human Diseases and Cancer, 239-246 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yanjun Lu: "Sites and types of UV-induced mutaions leading to inactivation of the qrowth-arresting activity in p21(sdil/cipl/wafl)cDNA." Carcinogenesis. 17. 2343-2345 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasuhiro Matsumura: "Characterization of p53 qene mutations in basal-cell carcinomas:comparison between sun-exposed andless-exposed skin areas." Int.J.Cancer. 65. 778-780 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Junji Miyakoshi: "Exposure to magnetic field(5mT at 60Hz)does not affect cell growth and c-myc gene expression." J.Radiat.Res.37. 185-191 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tomonari Matsuda: "Detection and quantification of DNA strand breaks n human cells induced by contaminants in Japanese tap waters." Wat.Sci.Tech.33. 297-304 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Junji Miyakoshi: "Increased radiosensitivity of p16 gene-deleted human glioma cells after transfection with wild-type p16 gene." Jpn.J.Cancer Res.88. 34-38 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Junji Miyakoshi: "Mutation induction by high-density,50 Hz magnetic field in human MeWo cells exposed in the DNA synthesis phase." Int.J.Radiat.Biol.71. 75-79 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasuhiro Matsumura: "High prevalence of mutations in the p53 gene in poorly differentiated squamous cell carcinomas in xeroderma pigmentosum patierts" J. Invest. Dermatol.105. 399-401 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Toshihiko Tsukada: "Vasoactive intestinal peptide gene expression in the rat pheochromocytoma cell line PC12" Mol. Cell. Endocrinol.107. 231-239 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tomonari Matsuda: "Molecular analysis of mutations induced by 2‐chloroacetaldehyde, the ultimate carcinogenic form of vinyl chloride, in human cells using shuttle vectors" Carcinog.16. 2389-2394 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Junji Miyakoshi: "Changes in radiation sensitivity of human osteosarcoma cells after p53 introduction" Jpn. J. Cancer Res.86. 711-713 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nobuyuki Yamagishi: "Modification of the radiosensitivity of human cells to which simian virus 40 T‐antigen was transfected" J. Radiat. Res.36. 239-247 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shuji Ohtsu: "Enhancement of β‐galactosidase gene expression in rat pheochromocytoma cells by exposure to extremely low frequency magnetic fields" Biochem. Biophys. Res. Commun.212. 104-109 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Toshihiko Tsukada: "Functional analysis of the cell-specific enhancer in the human proopiomelanocortin gene by β-galactosidase" DNA and Cell Biology. 13. 755-762 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Bokshil Shung: "X-ray-induced transcriptional activation of c-mos and XRCC1 genes in ataxia telangiectasia cells" Mutation Research. 307. 43-51 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Junji Miyakoshi: "A newly designed expreimental system for exposure of mammlian cells to extremely low frequency magnetic fields" Journal of Radiation Research. 35. 26-34 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takashi Yagi: "Similarity in the molecular profile of mutations induced by UV light in shuttle vector plasmids" Mutagenesis. 9. 73-77 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mayumi Sato: "Far less frequent mutations in ras genes than in p53 gene in skin tumors of xeroderma pigmentosum patients" Molecular Carcinogenesis. 11. 98-105 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chikako Nishigori: "Mutations in ras genes in cells cultured from mouse skin tumors induced by ultraviolet irradiation" Proceedings of the National Academy of Science of the United States. 91. 7189-7193 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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