Bolt H M, Kappus H, Kaufmann R, Appel K E, Buchter A, Bolt W
IARC Sci Publ (1971). 1976(13):151-63.
Rat liver microsomes metabolise 14 C-vinyl chloride to intermediates which irreversibly bind to the microsomal protein and to soluble proteins and RNA, when these compounds are added to the incubation. A superoxide (O2) generating system comprised of phenazine methosulfate and NADH also converts 14 C-vinyl chloride to metabolites which irreversibly bind to albumin. These data are consistent with the assumption of chloroethylene oxide being the primary reactive metabolite of vinyl chloride. If rats are exposed to 14 C-vinyl chloride, about half of the radioactive metabolites in the liver microsomal fraction is bound irreversibly to microsomal protein, when assessed immediately after exposure. Large amounts of polar, extractable, metabolites are present in the cytosol fraction. The amount of radioactivity in tissues of the rats, irreversibly bound immediately after exposure, comprises 10 - 40% of the total radioactivity in tissues. This percentage rises up to 70% after 48 hrs. Som radioactivity derived from 14 C-vinyl chloride is also incorporated into DNA and RNA of liver. Whereas the peak of incorporation of 14 C into DNA is already reached immediately after exposure to 14 C-vinyl chloride, specific labelling of RNA increases after exposure until its maximum after 24 hours.
当将这些化合物添加到孵育体系中时，大鼠肝脏微粒体会将14C-氯乙烯代谢为中间体，这些中间体可与微粒体蛋白、可溶性蛋白和RNA发生不可逆结合。由硫酸甲酯吩嗪和NADH组成的超氧化物（O2）生成系统也可将14C-氯乙烯转化为可与白蛋白发生不可逆结合的代谢产物。这些数据与环氧氯乙烷是氯乙烯主要活性代谢产物的假设一致。如果大鼠接触14C-氯乙烯，在接触后立即评估时，肝脏微粒体部分中约一半的放射性代谢产物会与微粒体蛋白发生不可逆结合。胞质溶胶部分存在大量极性、可提取的代谢产物。大鼠组织中在接触后立即发生不可逆结合的放射性物质的量占组织中总放射性的10%-40%。48小时后，这一百分比升至70%。源自14C-氯乙烯的一些放射性物质也会掺入肝脏的DNA和RNA中。虽然在接触14C-氯乙烯后立即达到14C掺入DNA的峰值，但RNA的特异性标记在接触后会增加，直到24小时后达到最大值。
