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首页> 美国政府科技报告 >Mechanisms of Radio-Resistance and Its Modification by Chemicals. Coordinated Programme on Improvement in Radiotherapy of Cancer Using Modifiers of Radiosensitivity of Cells. Final Report for the Period 1 July 1973 - 30 November 1
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Mechanisms of Radio-Resistance and Its Modification by Chemicals. Coordinated Programme on Improvement in Radiotherapy of Cancer Using Modifiers of Radiosensitivity of Cells. Final Report for the Period 1 July 1973 - 30 November 1

机译：耐化学机理及其化学改性。利用细胞放射敏感性改良剂改善癌症放射治疗的协调计划。 1973年7月1日至11月30日期间的最终报告

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Several membrane specific drugs have been tested for their radiosensitizing effects under hypoxia/anoxia using E.Coli cells. Among these chlorpromazine (CPZ) proved most effective. Investigations on its mechanism of action revealed partial involvement of radiolytic transients and its inhibitory effect on DNA repair and synthesis. A ''coctail'' consisting of CPZ and other drugs like procaine lignocaine, or telsacaine sensitized hypoxic bacteria beyond ''oxygen effect''. CPZ also showed preferential cytotoxicity to anoxic/hypoxic bacteria. Prolonged treatment of cells with CPZ under hypoxia at elevated temperatures (up to 39 exp 0 C) proved more lethal and the surviving cells showed extreme radiosensitivity (DMF=0.11). These results therefore wave situ extension of investigations to tumours. Two animal tumours viz a fibrosarcoma and sarcoma 180 were grown on Swiss mice. CPZ enhanced the radiation induced regression of these solid tumours. CPZ on its own showed chemotherapeutic effect and controlled the growth of these tumours. The chemotherapeutic effect was further enhanced at hyperthermic temperatures (41 and 42 exp 0 C). Pharmokinetic investigations on distribution and retention of CPZ in plasma, tumours and other organs have been completed using S-35 labelled CPZ. Clinical trials with human patients are being initiated. Attempts are also being made to target such drugs to tumour sites by. (Atomindex citation 14:727735)

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