1995 Fiscal Year Final Research Report Summary
Involvement of tumor suppresser genes in DNA repair
| Project/Area Number |
06454639
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
IHSIZAKI Kanji Aichi Cancer Center, Lab.Exp.Radiol., Head, 放射線部, 部長 (70111987)
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| Project Period (FY) |
1994 – 1995
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| Keywords | p53 gene / Checkpoint / DNA repair / SCE / supF gene / Mutation / Hot spot |
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| Research Abstract |
We established fibroblast cultures from the p53-deficient mouse embryos, which were originally constructed by Dr.S.Aizawa. These p53-deficient fibroblasts showed much increased growth rate compared with the wild-type homozygous and heterozygous cells. However, the p53-deficient fibroblasts showed the same sensitivity to UV and X-ray as the wild-type homozygous fibroblasts when analyzed by colony forming ability. We then analyzed removal of UV-induced DNA damages by using monoclonal antibody and there was no differnce between repair activity of pyrimidine dimmers and 6-4 photo products in the p53-deficient and proficient cells, either. However, delay of entering S-phase after UV-irradiation was significantly reduced in the p53-deficient cells, indicating some abnormality in the checkpoint function of the cell cycle in the p53-deficient cells. UV-induced sister chromatid exchanges were significantly increased in the p53-deficient cells, which suggests that DNA was replicated before removal of damages in the p53-deficient cells. We further analyzed changes of microsatellite sequences induced by UV in the p53-deficient and wild-type cells. Since the frequency of changes was not high enough, we could not detect any significant difference by analyzing about 100 clones of each cell on a fewloci. We also used the sup F gene on a shuttle vector to analyze UV-induced mutations in the p53-deficient and p53-proficient cells. UV-irradiated or non-irradiated shuttle vector plasmid carrying the sup F gene as a target of mutation (pYZ289) was introduced into p53-deficient and p53-proficient fibroblasts. Survival of UV-irradiated plasmid and the frequencies of UV-induced mutation of the sup F gene were the same in both types of cells. However, the distributions of base change mutations in the sup F sequence were different between p53-deficient and p53-proficient cells ; especially, locations of tandem CpC to TpT changes exhibited marked difference.
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[Publications] Ishizaki, K., Ejima, Y., Matsunaga.T., Hara, R., Sakamoto, A.Ikenaga, M., Ikawa, Y.and Aizawa, S.: "Increased UV-induced SCEs but normal repair of DNA damage in p53-deficient mouse cells." Int.J.Cancer. 58. 254-257 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Fujikawa, K., Ayaki, H., Ishizaki, K., Takatera, H., Matsuo, S., Iizaja, H., Koizumi, H.and Ikenaga, M.: "Assignment of six patients with xeroderma pigmentosum in Hokkaido area to a variant form." J.Radiat.Res.35. 168-178 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Kato, T.Jr., Todo, T., Ayaki, H., Ishizaki, K., Morita, T., Mitra, S.and Ikenaga, M.: "Cloning of a marsupial DNA photolyase gene and lack of related nucleotide sequences in placental mammals." Nucleic Acids Res.22. 4119-4124 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Shibagaki, I., Tanaka, H., Shimada, Y., Wagata, T., Ikenage, M., Imamura, M.and Ishizaki, K.: "p53 mutation, murine double minute2 amplification and human papillomavirus infection are frequently involved but no associated with each other in esophageal squamous cell carcinoma." Clinical Cancer Research. 1. 769-773 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Tanaka, H., Shibagaki, I., Shimada, Y., Wagata, T., Imamura, M.and Ishizaki, K.: "Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines : Increased frequency and different spectrum of mutations from primary tumors." Int.J.Cancer. 65. 372-376 (1996)
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「研究成果報告書概要(欧文)」より
