| Research Abstract |
During 1998-2000, we have investigated on the identification of genes determining radiosensitivities of tumors in hi vitro and in vivo based on the observation that the radiosensitivity of two tumors had shown the dessociation between in vitro and in vivo. In order to clone novel human genomes responsible for the radiosensitivities of tumors, we adopted novel methodology, that is,modified degenerative primer technique. Using this, we have successsfully cloned 4 novel human genomes which might be associated with cell cycle or cell adgesion.
On the other hand, we have found that the cellular radiosensitivities of tumor cells which are not equivalent to the ones of original histologies may not differ from each other irrespective of p53 status. Then, weinvestigated the oxygen tension in 10 different human malignancies xenografts. Successfully we have demonstrated the correlation between the tumor radiosensitivities and their oxygen tension. As for the molecular mechanisms of the hypoxia issue, we adopted RT-PCR methods using primers of coagulation/fibrinolytic and angiogenesis factors such as PAI-1. Successfully we have demonstrated that the mRNA expression of these factors at the tissue level are more relevant to the tumor hypoxia rather than those at the cellualr level. In conclusion, the radiosensitivities of tumors in in vitro and in vivo may be determined by the different mechanisms, that is, the gene expression of different genes.
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