Bronzetti G, Bauer C, Corsi C, Del Carratore R, Galli A, Nieri R, Paolini M, Cundari E, Cantelli Forti G, Crenshaw J
Teratog Carcinog Mutagen. 1984;4(4):365-75. doi: 10.1002/tcm.1770040406.
The cis and trans isomers of 1,2-dichloroethylene were tested for mutagenic effects in a diploid strain (D7) of the yeast Saccharomyces cerevisiae in suspension tests with and without a mammalian microsomal activation system, an S9 mouse liver fraction, and by an in vivo intrasanguineous host mediated assay. The effects of the same agents on aminopyrine N-demethylase activity and cytochrome P-450 level in liver were studied in nonpretreated and in phenobarbital + beta-naphtoflavone-pretreated mice. In the suspension test, both isomers exhibited dose dependent toxicity, and survival was lower with metabolic activation than without. In this test also, both isomers exhibited genetic activity as measured by increases in recombinants at the ade 2 locus in experiments with metabolic activation. In the host-mediated assay, only the cis isomer showed evidence of mutagenic activity with significant increases in convertants at the trp locus and revertants at the ilv locus. Such mutagenic activity was found both after acute and chronic doses and in liver, kidney, and lung tissue. The two isomers exhibited different effects with respect to aminopyrine N-demethylase activity and cytochrome P-450 level. In general, the trans isomer appeared to emphasize induction of enzyme activity or level while the cis isomer more frequently tended to inhibit activity or destroy the enzyme.
在有和没有哺乳动物微粒体激活系统(S9小鼠肝脏组分)的悬浮试验中,以及通过体内血内宿主介导试验,对1,2 - 二氯乙烯的顺式和反式异构体在酿酒酵母的二倍体菌株(D7)中进行了诱变效应测试。在未经预处理以及经苯巴比妥 + β - 萘黄酮预处理的小鼠中,研究了相同试剂对肝脏中氨基比林N - 脱甲基酶活性和细胞色素P - 450水平的影响。在悬浮试验中,两种异构体均表现出剂量依赖性毒性,并且代谢激活时的存活率低于未激活时。在该试验中,通过代谢激活实验中ade 2位点重组体的增加来衡量,两种异构体也均表现出遗传活性。在宿主介导试验中,只有顺式异构体显示出诱变活性的证据,在trp位点的转化体和ilv位点的回复体显著增加。急性和慢性剂量后以及在肝脏、肾脏和肺组织中均发现了这种诱变活性。两种异构体在氨基比林N - 脱甲基酶活性和细胞色素P - 450水平方面表现出不同的影响。一般来说,反式异构体似乎更强调酶活性或水平的诱导,而顺式异构体更频繁地倾向于抑制活性或破坏酶。