The Effect of Caffeine on p53-Dependent Radioresponses in Undifferentiated Mouse Embryonal Carcinoma Cells after X-ray and UV-irradiations

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概要

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• The effect of caffeine was studied on the radioresponses of undifferentiated mouse embryonal carcinoma cells (EC cells) with or without the functional p53. The radioresponses studied included radiosensitivity, the activation of p53, apoptosis with characteristic DNA ladder formation and cell cycle progression. An undifferentiated mouse EC cell line, ECA2, and a newly established p53-deficient EC cell line, p53δ, were used in the present study. The status of the p53 gene did not significantly affect the colony survivals of undifferentiated EC cells to X-rays and UV. Although a post-irradiation treatment with caffeine sensitized both lines to X-rays marginally, the sensitization was prominent for UV regardless of the p53 status of the cells. The activation of a p53 responsible lacZ reporter construct was observed in stably transfected ECA2 cells after X-ray and UV irradiations. Caffeine suppressed the X-ray induced activation of the lacZ reporter, while it drastically enhanced the activation after UV irradiation. X-rays and UV readily triggered the apoptosis of ECA2 cells with the characteristic DNA ladder. Although UV-induced DNA ladder formation was enhanced by caffeine, that induced by X-rays was unaffected. Therefore, the effects of caffeine on the p53-dependent radioresponses were found to be agent specific: suppression for the X-ray induced and augmentation for the UV induced. In contrast to p53- proficient ECA2 cells, smear-like DNA degradation was observed for irradiated p53δ cells, suggesting the presence of a mode of cell death without DNA ladder formation. UV induction of the smear-like DNA degradation was enhanced in the presence of caffeine. Regardless of the state of the p53 gene, G1/ S arrest was not observed in X-ray and UV irradiated EC cells. X-rays induced G2/M arrest in both lines, which was abrogated by caffeine, while G2/M arrest after UV was unaffected by a caffeine treatment. These results indicate that the radioresponses of undifferentiated EC cells differ considerably from those of somatic cells, and that these radioresponses were modulated by a post-irradiation treatment with caffeine.

• 日本放射線影響学会の論文

著者

• SHIMURA Tsutomu

  Institute of Industrial Science, University of Tokyo

• Oshimura Mitsuo

  Department of Molecular and Cell Genetics, School of Life Science, Faculty of Medicine, Tottori Univ

• Kimura Shinzo

  Environ. Radiat. Protect. Group Nirs

• SHIMURA Tsutomu

  Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University

• Shimura Tsutomu

  Kyoto University Radiation Biology Center

• Shimura Tsutomu

  京都大学放射線生物研究センター

• Shimura Tsutomu

  Department Of Pathology Institute Of Development Aging And Cancer Tohoku University

• AIZAWA Shinichi

  Department of Morphogenesis, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto Univers

• Niwa Ohtsura

  Kyoto Univ. Radiation Biology Center

• Shimura Tsutomu

  Radiation Biology Center Kyoto Univ.

• Oshimura M

  Tottori Univ. Yonago Jpn

• Oshimura Mitsuo

  鳥取大学 医学部分子細胞生物学講座ゲノム医工学分野

• Oshimura Mitsuo

  Department Of Biomedical Science Graduate School Of Medical Science Tottori University

• TAGA Masataka

  Department of Late Effect Studies, Radiation Biology Centet Kyoto University

• SHIRAISHI Kazunori

  Department of Late Effect Studies, Radiation Biology Centet Kyoto University

• UEMATSU Norio

  Department of Late Effect Studies, Radiation Biology Centet Kyoto University

• NIWA Ohtsura

  Department of Late Effect Studies, Radiation Biology Centet Kyoto University

• KATO TOMOHISA

  Department of Late Effect Studies and Department of System Biology, Radiation Biology Center, Kyoto

• NISHIMUNE YOSHITAKE

  Department of Science for Laboratory Animal Experimentation, Research Institute for Microbial Diseas

• Niwa O

  Kyoto Univ. Kyoto

• 白石 久二雄

  Department Of Radiation Dosimetry National Institute Of Radiological Sciences (nirs)

• SHIRAISHI Kei

  Department of Pathology

• Ojima Mitsuaki

  Division Of Molecular Genetics And Biofunction Department Of Biomedical Science Institute Of Regener

• Aizawa Shinichi

  Vertebrate Body Plan Group Riken Center Of Developmental Biology

• Aizawa Shinichi

  Department Of Morphogenesis Institute Of Molecular Embryology And Genetics School Of Medicine Kumamo

• Niwa O

  Research Institute For Nuclear Medicine And Biology Hiroshima University

• Niwa Ohtsura

  Res. Inst. Radiat. Biol. Med. Hiroshima Univ.

• Niwa Ohtsura

  Department Of Immunology. Radiation Biology Center. Kyoto University

• Taga Masataka

  京都大学放射線生物研究センター

• Taga Masataka

  Dept Of Radiobiology Radiat. Effect Res. Foundation

• Uematsu N

  Tohoku Univ. Miyagi Jpn

• Uematsu Norio

  Department Of Biomolecular Sciences Graduate School Of Life Sciences Tohoku University

• Kato Tomohisa

  Department Of Late Effect Studies And Department Of System Biology Radiation Biology Center Kyoto Un

• Nishimune Y

  Osaka Univ. Osaka Jpn

• Aizawa Shinichi

  Department Of Morphogenesis Institute Of Molecular Embryology And Genetics Kumamoto University

• Niwa Ohtsura

  Res. Inst. Nuc. Ned. Biol. Hiroshima Univ.

• Shimura Tsutomu

  Radiat. Biol. Center. Kyoto. Univ.

• Nishimune Yoshitake

  Department Of Science For Laboratory Animal Experimentation Research Institute For Microbial Diseases Osaka University

• Nishimune Yoshitake

  Department of Molecular Embryology, Research Institute for Microbial Diseases, Osaka University

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