| Radioimmunotherapy(RIT), as an option of radiotherapy, play a role in cancer treatment. In addition to its effect on tumor by targeting tumor cells specifically by conjugating cell toxins to tumor-specific antibodies, its continuous low-dose-rate effect characterized in its irradiation on tumor tissue with a relative low side-effect on normal tissue could not be ignored. The radiobiological mechanism underlying KIT especially in its long-term low-dose-rate effect on tumor cells is not clear. Highly expressing telomerase is considered as a distinguished biochemical feature of the malignant phenotype that could be a potential anti-cancer target for enhancing the effectiveness of radiotherapy, or as a measure for monitoring radiocurability. This study will focus on two aspects:1. To elucidate the radiobiological mechanism underlying cancer treatment of low-dose-rate p-irradiation of 32P, meanwhile comparing cell-killing pattern with high-dose-rate y-irradiation of ^Co.2. To investigate whether telomerase activity can be a measure for monitoring radiocurability or whether the intrinsic telomerase activity can be a marker to predict radiosensitivity of tumor cells. To investigate how the telomerase inhibitor influence the outcome of radiotherapy.The study of the radiobiological mechanism underlying low-dose-rate (3-irradiatioD of 32P. HeLa cells were exposed to low-rate irradiation of 32P or high-dose-rate y-irradiation of ^Co. Cell response-patterns were compared between two types of radiations, focusing on the relation of different type of radiation to growth arrest?radiation-induced senescence, and apoptotic cell death evaluated by X-gal senescence staining, flow cytometry and typanblue excluded method respectively. Long-term post-irradiation effects on tumor cells such as morphological and proliferation changes, chromosome aberrations and telomerase activity were evaluated by X-gal senescence staining, [3H] thymidine incorporation, chromosome Giemsa staining and TRAP-ELISA methods respectively. Data showed that there is a similar cell inhibition effect on HeLa cells between the radiation of 32P at dose-rate 0.375cGy/min and that of ^Coy at dose-rate of 206cGy/min by the time of 72h post-radiation but in a different way of cell killing. In exposure to 32P, more HeLa cells go to reproductive cell death, being eliminated by apoptosis than to 60Co. Cell cycle arrest in G2 phase induced by 32P was 50% lower and more prolong than that induced by 60Co(80%). X-gal staining showed that senescent cell ratio hi Hela cells after exposure of 32P was higher than ^Co. Although the total cell-death number in HeLa cells after irradiation of ^Co was higher than that of 32P, the difference in the final inhibition effect on tumor cells between the two types of radiation was reduced. It is suggested that there is more reproductive cell death contributing to total cell death in HeLa cells by radiation of 32P. Impaired DNA repair system by continuous low-dose-rate radiation might contribute to the final radiation effect of 32P.Long-term radiation effect At 30th day post-irradiation, there remained some morphological changes in HeLa cells that had survived radiations with the phenotype of delayed reproductive death, which included an increased fraction of cells with giant, aneuploidy and multinucleated cell phenotypes characterizing by positive-staining ofX-gal. Both proliferation ratio measured by [3H] thymidine incorporation and telomerase activity in HeLa cells survived radiation remain lower than in control cells. Chromosome- aberration-ratio analyzed by Giemsa staining method in survived HeLa cells was higher than in control cells. All these changes were in a dose-dependant manner. It seems like that chromosome instability as a result of DNA damage induced by radiation contribute to the senescence-like phenotype in HeLa cell survived radiation that cause lower proliferation ratio and telomerase activity. In the other hand, telomerase activity may be inhibited by irradiation directly through a c-Abl dependan...
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