Sinsheimer J E, Chen R, Das S K, Hooberman B H, Osorio S, You Z
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Mutat Res. 1993 Jan;298(3):197-206. doi: 10.1016/0165-1218(93)90041-b.
The (R)- and (S)-optical isomers of 9 epoxides, benzyloxymethyloxirane, epichlorohydrin, glycidol, glycidyl 3-nitrobenzenesulfonate, glycidyl 4-nitrobenzoate, glycidyl tosylate, styrene oxide, glycidyl 1-naphthyl ether and glycidyl 4-nitrophenyl ether, have been compared for their in vivo and in vitro genotoxicity. The in vitro short-term test employed was the Ames mutagenicity assay with Salmonella strain TA100. The in vivo tests were chromosomal aberrations (CA) as well as sister-chromatid exchange (SCE) in bone-marrow cells of mice following intraperitoneal administration of these epoxides. Differences in mutagenicity between isomers were established with TA100 for all the compounds. While 13 of the isomers were genotoxic compared to a negative control by CA measurements, only in the case of glycidyl 4-nitrobenzoate could a significant difference be found between isomers by this test. However, with SCE evaluations, differences were detected between the (R)- and (S)-isomers for all the pairs of compounds with the exception of those for benzyloxymethyloxirane and glycidyl 4-nitrophenyl ether. At least in part, differences in the patterns of genotoxicity among compounds can be related to their differences in reaction pathways.
对9种环氧化合物的（R）-和（S）-光学异构体，即苄氧基甲基环氧乙烷、环氧氯丙烷、缩水甘油、对甲苯磺酸缩水甘油酯、4-硝基苯甲酸缩水甘油酯、对甲苯磺酸缩水甘油酯、氧化苯乙烯、1-萘基缩水甘油醚和4-硝基苯基缩水甘油醚的体内和体外遗传毒性进行了比较。所采用的体外短期试验是用鼠伤寒沙门氏菌TA100菌株进行的艾姆斯诱变试验。体内试验是在给小鼠腹腔注射这些环氧化合物后，检测其骨髓细胞中的染色体畸变（CA）以及姐妹染色单体交换（SCE）。通过TA100确定了所有化合物异构体之间的诱变性差异。与阴性对照相比，通过CA测量发现13种异构体具有遗传毒性，只有在4-硝基苯甲酸缩水甘油酯的情况下，通过该试验才能发现异构体之间存在显著差异。然而，通过SCE评估，除苄氧基甲基环氧乙烷和4-硝基苯基缩水甘油醚外，所有化合物对的（R）-和（S）-异构体之间均检测到差异。化合物之间遗传毒性模式的差异至少部分与其反应途径的差异有关。
