細胞の老化と不死化の接点

DOI
  • 加納 良男
    岡山大学医学部分子細胞医学研究施設細胞生物
  • 遠藤 彰
    岡山大学医学部分子細胞医学研究施設細胞生物
  • 難波 正義
    岡山大学医学部分子細胞医学研究施設細胞生物

書誌事項

タイトル別名
  • RELATION OF CELLULAR AGING AND IMMORTALIZATION

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Immortalization of human cells is associated with the process of cellular aging. Normal human fibroblasts are exceedingly resistant to in vitro malignant transformation by chemical carcinogens, radiation or oncogenic viruses. This may be due to difficulty of human fibroblasts to be immortalized in culture. The nuclear oncogenes such as myc, p53 and SV4OT dominantly immortalize murine cells, but these genes can not immortalize human cells.<br>We obtained two types of immortalization sensitive cells from fibroblasts of Wilms' tumor patients having chromosome lip deletion. They showed 7-fold and 50-fold frequency of immortalization over normal human fibroblasts by SV4OT, respectively. Both types of the cells which produced SV4OT protein showed the abnormal crisis, whereas T-antigen positive normal cells did not. We found out that the cells at this abnormal crisis showed an extremely high frequency of the spontaneous mutation (6IGs→6TGr). These results indicated that when these cells entered the senescence period, activation of senescence genes probably occurred, resulting in inhibition of cell proliferation, and leading to crisis and mutation.<br>Based on the present results, we suppose that if strong oncogenes are expressed at this senescence stage, competition between growth inhibitory effects of senescence gene and growth stimulatory effects of oncogene products will occur in the cells, and mutational events will be accelerated in these aging cells. Senescence genes are also supposed to be mutated at the crisis period. If both copies of senescence genes on homologous chromosomes are inactivated by mutation, normal human cells will be immortalized.

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