Molecular analysis of the role of p53 in radioadaptive response

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15510047
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kyoto University
• Principal Investigator: TACHIBANA Akira Kyoto University, Radiation Biology Center, Associate Professor, 放射線生物研究センター, 助教授 (20188262)
• Co-Investigator(Kenkyū-buntansha): TODO Takeshi Kyoto University, Radiation Biology Center, Professor, 放射線生物研究センター, 教授 (90163948)
• Project Period (FY): 2003 – 2005
• Keywords: radioadaptive response / low-dose radiation / DNA double-strand break / p53 / end-joining / mutagenesis

Research Abstract

Radioadaptive response is a biological defense mechanism that is induced by low-dose ionizing irradiation for cellular resistance to the genotoxic effects of subsequent irradiation. Nuclear extracts were prepared from unirradiated cells (unirradiated extract), cells exposed to either 2 cGy (2 cGy extract) or 3 Gy (3 Gy extract) of X-rays, and cells pre-exposed with 2 cGy and then challenged with 3 Gy (2 cGy+3 Gy extract). The efficiency of end joining by the 3 Gy extract was somewhat reduced, but the rejoining efficiency of the 2 cGy+3 Gy extract was similar to the efficiency of the unirradiated extract. The fidelity of end-joining was estimated from the frequency of mutant plasmids. The mutant frequency by the 3 Gy extract was higher than the unirradiated level. But, the mutant frequency by the 2 cGy+3 Gy extract was about half of the unirradiated level, indicatinging high fidelity of rejoining. Moreover, we have demonstrated that the radioadaptive response is absent in p53-deficient mouse cells. We examined the end-joining reaction using the extracts isolated from p53-deficient mouse cells irradiated with X-rays with or without pre-irradiation. No change was observed either in the efficiency or in the fidelity of end-joining irrespective of pre-irradiation. Therefore, p53 could be an important regulatory factor of end-joining in radioadaptive response. We further examined mutations induced by ionizing radiation with or without radioadaptive response at the Hprt locus in mouse m5S cells. We analyzed the Hprt gene in 6-thioguanine-resistant mutants by amplification of all the nine exons of the mouse Hprt gene. Our results showed that the proportion of partial deletions was much higher in mutants isolated from the pre-exposed radioadaptive culture than in non-primed irradiated culture.

Research Products

• [Journal Article] DNA repair defect in AT cells and their hypersensitivity to low-dose-rate radiation. (2006)
  • Author(s): Nakamura, H., Yasui, Y., Saito, N., Tachibana, A., Komatsu, K., Ishizaki, K.
  • Journal Title: Radiation Research 165 (3) Pages: 277-282
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DNA repair defect in AT cells and their hypersensitivity to low-dose-rate radiation. (2006)
  • Author(s): Nakamura, H., Yasui, Y., Saito, N., Tachibana A., Komatsu, K., Ishizaki, K.
  • Journal Title: Radiation Research 165(3) Pages: 277-282
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli. (2005)
  • Author(s): Chang, P.-W., Zhang, Q.-M., Takatori, K., Tachibana, A., Yonei, S.
  • Journal Title: International Journal of Radiation Biology 81 (2) Pages: 115-123
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cytotoxic and mutagenic effects of chronic low-dose-rate irradiation on TERT-immortalized human cells. (2005)
  • Author(s): Nakamura, H., Fukami, H., Hayashi, Y., Tachibana, A., Nakatsugawa, S., Hamaguchi, M., Ishizaki, K.
  • Journal Title: Radiation Research 163 (3) Pages: 283-288
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli. (2005)
  • Author(s): Chang, P.-W., Zhang, Q.-M., Takatori, K., Tachibana.A., Yonei, S.
  • Journal Title: International Journal of Radiation Biology 81(2) Pages: 115-123
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cytotoxic and mutagenic effects of chronic low-dose-rate irradiation on TERT-immortalized human cells. (2005)
  • Author(s): Nakamura, H., Fukami, H., Hayashi, Y., Tachibana, A., Nakatsugawa, S., Hamaguchi, M., Ishizaki, K.
  • Journal Title: Radiation Research 163(3) Pages: 283-288
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Stress induced premature senescence in hTERT-expressing ataxia telangiectasia fibroblasts. (2004)
  • Author(s): Naka, K., Tachibana, A., Ikeda, K., Motoyama, N.
  • Journal Title: Journal of Biological Chemistry 279 (39) Pages: 2030-2037
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Recombination repair pathway in the maintenance of chromosomal integrity against DNA interstrand crosslinks. (2004)
  • Author(s): Sasaki, M.S., Takata, M., Sonoda, E., Tachibana, A., Takeda, S.
  • Journal Title: Cytogenetic and Genome Research 104 (1-49) Pages: 28-34
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Low transposition frequency of the medaka fish To12 element may be due to extranuclear localization of its transposase. (2004)
  • Author(s): Iida, A., Tachibana, A., Hamada, S., Hori, H., Koga, A
  • Journal Title: Genes and Genetic Systems 79 (2) Pages: 119-124
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic and physiological regulation of non-homologous end-joining in mammalian cells. (2004)
  • Author(s): Tachibana, A.
  • Journal Title: Advances in Biophysics 38 Pages: 21-44
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] No induction of p53 phosphorylation and few focus formation of phosphorylated H2AX suggest efficient repair of DNA damage during chronic low-dose-rate irradiation in human cells. (2004)
  • Author(s): Ishizaki, K., Hayashi, Y., Nakamura, H., Yasui, Y., Komatsu, K., Tachibana, A.
  • Journal Title: Journal of Radiation Research 45 (4) Pages: 521-525
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Stress induced premature senescence in hTERT expressing ataxia telangiectasia fibroblasts. (2004)
  • Author(s): Naka, K., Tachibana, A., Ikeda, K., Motoyama, N.
  • Journal Title: Journal of Biological Chemistry 279(3) Pages: 2030-2037
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Recombination repair pathway in the maintenance of chromosomal integrity against DNA interstrand crosslinks. (2004)
  • Author(s): Sasaki, M.S., Takata, M., Sonoda, E., Tachibana.A., Takeda, S.
  • Journal Title: Cytogenetic and Genome Research 104(1-4) Pages: 28-34
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Low transposition frequency of the medaka fish Tol2 element may be due to extranuclear localization of its transposase. (2004)
  • Author(s): Iida, A., Tachibana, A., Hamada, S., Hori, H., Koga, A.
  • Journal Title: Genes and Genetic Systems 79(2) Pages: 119-124
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genetic and physiological regulation of non-homologous end joining in mammalian cells. (2004)
  • Author(s): Tachibana, A.
  • Journal Title: Advances in Biophysics 38 Pages: 21-44
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] No induction of p53 phosphorylation and few focus formation of phosphorylated H2AX suggest efficient repair of DNA damage during chronic low-dose-rate irradiation in human cells. (2004)
  • Author(s): Ishizaki, K., Hayashi, Y., Nakamura, H., Yasui, Y., Komatsu, K., Tachibana, A.
  • Journal Title: Journal of Radiation Research 45(4) Pages: 521-525
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The medaka fish Tol2 transposable element can undergo excision in human and mouse cells. (2003)
  • Author(s): Koga, A., Iida, A., Kamiya, M., Hayashi, R., Hori, H., Ishikawa, Y., Tachibana, A.
  • Journal Title: Journal of Human Genetics 48 (5) Pages: 231-235
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The medaka fish Tol2 transposable element can undergo excision in human and mouse cells. (2003)
  • Author(s): Koga, A., Iida, A., Kamiya, M., Hayashi, R., Hori, H., Ishikawa, Y., Tachibana, A.
  • Journal Title: Journal of Human Genetics 48(5) Pages: 231-235
  • Description: 「研究成果報告書概要(欧文)」より