MOLECULAR RADIOBIOLOGY OF HUMAN CELL LINES. V. COMPARATIVE RADIOSENSITIZING PROPERTIES OF 5-HALODEOXYCYTIDINES AND 5-HALODEOXYURIDINES.
MOLECULAR RADIOBIOLOGY OF HUMAN CELL LINES. V. COMPARATIVE RADIOSENSITIZING PROPERTIES OF 5-HALODEOXYCYTIDINES AND 5-HALODEOXYURIDINES.
复制标题
人类细胞系的分子放射生物学。
作者：
R. Erikson;W. Szybalski
已经反复证明，掺入5-卤代脱氧尿苷（胸苷的结构类似物）显著增加了转化DNA（1，2）、噬菌体（3-5）、细菌（6-9）和动物细胞（10，11）的辐射敏感性。当卤代脱氧胞苷变得可用（12，13），并显示也被掺入DNA（14-18），它们的放射增敏特性与胸苷类似物进行了比较。由于5-卤代脱氧胞苷可能仅在先前代谢转化为相应的5-卤代脱氧尿苷后才掺入DNA中（14-18），因此放射增敏程度应主要反映这些类似物的相对代谢稳定性及其掺入DNA前脱氨基的效率。另一方面，本研究独立检查了放射增敏程度与胸苷替代程度之间的关系（9），以及紫外线和X射线增敏机制之间差异的早期迹象; 5-溴脱氧尿苷是迄今为止最有效的紫外线增敏剂，5-碘脱氧尿苷是最有效的X射线增敏剂（11）。具体地，比较了5-溴脱氧尿苷（BUdR）、5-溴脱氧胞苷（BCdR）、5-碘脱氧尿苷（IUdR）和5-碘脱氧胞苷（ICdR）掺入培养的人细胞DNA的程度，与标记细胞对各种能量水平的紫外线和X射线的敏感性有关。
It has been demonstrated repeatedly that incorporation of 5-halodeoxyuridines, structural analogs of thymidine, markedly augments the radiation sensitivity of transforming DNA (1, 2), bacteriophages (3-5), bacteria (6-9), and animal cells (10, 11). When the halogenated deoxycytidines became available (12, 13) and were shown also to be incorporated into DNA (14-18), a comparison of their radiosensitizing properties with those of the thymidine analogs was undertaken. Since the 5-halodeoxycytidines are incorporated into DNA presumably only after previous metabolic conversion to the corresponding 5-halodeoxyuridines (14-18), the degree of radiosensitization should reflect mainly the comparative metabolic stability of these analogs and the efficiency of their deamination prior to incorporation into DNA. On the other hand, this study constituted an independent check on the relationship between the degree of radiosensitization and the extent of thymidine replacement (9), as well as on the earlier indications of a discrepancy between the ultraviolet light and X-ray sensitization mechanisms; 5-bromodeoxyuridine was by far the most effective ultraviolet light sensitizer, and 5-iododeoxyuridine was the most effective X-ray sensitizer (11). Specifically, a comparison was made between the degrees of incorporation of 5-bromodeoxyuridine (BUdR), 5-bromodeoxycytidine (BCdR), 5-iododeoxyuridine (IUdR), and 5-iododeoxycytidine (ICdR) into the DNA of cultured human cells, as related to the sensitivity of the labeled cells toward ultraviolet light and X-rays of various energy levels.