Costa A K, Ivanetich K M
Carcinogenesis. 1984 Dec;5(12):1629-36. doi: 10.1093/carcin/5.12.1629.
The major initial metabolites of the chlorinated ethylenes in hepatocyte suspensions isolated from phenobarbital treated rats were as follows (rates of metabolite production in nmol/10(6) cells/min are given in brackets): vinylidene chloride, dichloroacetic acid (0.015); cis-1,2-dichloroethylene, 2,2-dichloroethanol (0.24); trans-1,2-dichloroethylene, dichloroacetic acid (0.005); trichloroethylene, chloral hydrate (2.7); tetrachloroethylene, trichloroacetic acid (0.08). Comparison of the metabolism of the chlorinated ethylenes by isolated hepatocyte suspensions and hepatic microsomes indicates that the initial products of the three dichlorinated ethylenes from cytochrome P-450 in hepatic microsomes are rapidly and extensively metabolized in the hepatocyte, where the Phase II enzymes are present. In contrast, the initial metabolites of trichloroethylene and of tetrachloroethylene in the two systems are identical. The abilities of the chlorinated ethylenes to induce unscheduled DNA synthesis was assessed in isolated hepatocytes using a method which does not require the blocking of semi-conservative DNA synthesis. Vinylidene chloride, cis-1,2-dichloroethylene and trichloroethylene induced unscheduled DNA synthesis, while trans-1,2-dichloroethylene and tetrachloroethylene did not.
从经苯巴比妥处理的大鼠分离出的肝细胞悬液中，氯化乙烯的主要初始代谢产物如下（括号内给出的是代谢产物生成速率，单位为nmol/10⁶细胞/分钟）：偏二氯乙烯，二氯乙酸（0.015）；顺式1,2 - 二氯乙烯，2,2 - 二氯乙醇（0.24）；反式1,2 - 二氯乙烯，二氯乙酸（0.005）；三氯乙烯，水合氯醛（2.7）；四氯乙烯，三氯乙酸（0.08）。对分离的肝细胞悬液和肝微粒体中氯化乙烯代谢情况的比较表明，肝微粒体中细胞色素P - 450作用于三种二氯乙烯的初始产物在含有II相酶的肝细胞中会迅速且大量地代谢。相比之下，两种体系中三氯乙烯和四氯乙烯的初始代谢产物是相同的。使用一种无需阻断半保留DNA合成的方法，在分离的肝细胞中评估了氯化乙烯诱导非定标DNA合成的能力。偏二氯乙烯、顺式1,2 - 二氯乙烯和三氯乙烯可诱导非定标DNA合成，而反式1,2 - 二氯乙烯和四氯乙烯则不能。
