Castro G D, Díaz Gómez M I, Castro J A
Centro de Investigaciones Toxicológicas CITEFA/CONICET, Buenos Aires, Argentina.
Cancer Lett. 1990 Aug;53(1):9-15. doi: 10.1016/0304-3835(90)90004-h.
Liver nuclear preparations from male Syrian Golden hamster (SG); C3H mice and Sprague-Dawley (SD) rats were able to biotransform CCl4 to CHCl3. That ability was not NADPH dependent and proceeded to an equal extent under N2 or air. Studies in more detail with C3H mice preparations revealed that only one of the processes was of an enzymatic nature and that it was inhibited by 1 mM EDTA. There was a correlation between liver nuclear ability to biotransform CCl4 to CHCl3 in the species tested and their liver carcinogenic response to CCl4. That correlation was not observed when biotransformation was studied using liver slices instead of liver nuclei. Liver nuclear preparations from the 3 species were able to promote a lipid peroxidation (LP) process in the presence of CCl4. The process was fully NADPH dependent in the case of SG and SD preparations but not in C3H mice. Study of the process in detail in the case of C3H mice shows that in that case LP was heat and EDTA sensitive, particularly in the absence of NADPH. There was no correlation between the intensity of CCl4 promoted LP either in liver nuclear or liver slices preparations in the 3 species tested and their carcino genic response to CCl4. Results might suggest that LP does not determine or rate limit the process of cancer development by CCl4 but do not exclude its participation in a given stage of the overall process.
来自雄性叙利亚金仓鼠(SG)、C3H小鼠和斯普拉格-道利(SD)大鼠的肝核制剂能够将四氯化碳生物转化为三氯甲烷。该能力不依赖于NADPH,并且在氮气或空气中以相同程度进行。对C3H小鼠制剂进行的更详细研究表明,只有一个过程是酶促性质的,并且它受到1 mM EDTA的抑制。在所测试的物种中,肝核将四氯化碳生物转化为三氯甲烷的能力与其对四氯化碳的肝脏致癌反应之间存在相关性。当使用肝切片而非肝核研究生物转化时,未观察到这种相关性。来自这3个物种的肝核制剂在存在四氯化碳的情况下能够促进脂质过氧化(LP)过程。在SG和SD制剂的情况下,该过程完全依赖于NADPH,但在C3H小鼠中则不然。对C3H小鼠的该过程进行详细研究表明,在这种情况下,LP对热和EDTA敏感,尤其是在没有NADPH的情况下。在所测试的3个物种的肝核或肝切片制剂中,四氯化碳促进的LP强度与其对四氯化碳的致癌反应之间没有相关性。结果可能表明,LP并不决定或限制四氯化碳致癌发展过程,但不排除其参与整个过程的特定阶段。