Kostoryz Elisabet L, Smith Robert E, Glaros Alan G, Chappelow Cecil C, Eick J David
School of Pharmacy, University of Missouri, 2411 Holmes Street, Kansas City 64108-2792, USA.
Mutat Res. 2004 Sep 12;563(1):25-34. doi: 10.1016/j.mrgentox.2004.05.013.
Cyracure UVR 6105 is a cycloaliphatic epoxy monomer and has both carboxylate and epoxy groups, with the potential for rapid polymerization. It is widely used in industry for the preparation of inks, resins, coatings, and was proposed for incorporation into dental composites. The objective of this study was to determine the mutagenic potential of this chemical related to its metabolite products. Several doses of Cyracure UVR 6105 were dissolved in DMSO and subjected to the Ames Salmonella mutagenicity assay. A metabolic activation system (S9-mix) was used consisting of Arochlor-induced liver S9 homogenate enriched with NADP and glucose-6-phosphate cofactors. In contrast to studies without S9-mix, Cyracure UVR 6105 exhibited enhanced genotoxic activities with strains TA100 and TA1535 in the presence of liver S9-mix. From in vitro metabolism of Cyracure UVR 6105 with S9-mix, as used in the Ames assay, several metabolites were identified. The alcohol metabolite, 3,4-epoxycyclohexylmethanol, containing intact epoxy group was identified in the organic solvent extract. This metabolite was synthesized and proved to be mutagenic against TA100 when assayed in the presence and absence of S9-mix. Results showed that the increased mutagenicity of Cyracure UVR-6105 in the presence of liver enzymes is due to the formation of the mutagenic metabolite 3,4-epoxycyclohexylmethanol.
Cyracure UVR 6105是一种脂环族环氧单体，同时含有羧基和环氧基团，具有快速聚合的潜力。它在工业上广泛用于制备油墨、树脂、涂料，并被提议用于牙科复合材料中。本研究的目的是确定这种化学物质与其代谢产物相关的致突变潜力。将几种剂量的Cyracure UVR 6105溶解在二甲基亚砜（DMSO）中，并进行艾姆斯沙门氏菌致突变性试验。使用了一种代谢活化系统（S9混合物），该系统由富含烟酰胺腺嘌呤二核苷酸磷酸（NADP）和葡萄糖-6-磷酸辅因子的艾氏剂诱导的肝脏S9匀浆组成。与没有S9混合物的研究相反，在肝脏S9混合物存在的情况下，Cyracure UVR 6105在TA100和TA1535菌株中表现出增强的遗传毒性活性。从用于艾姆斯试验的Cyracure UVR 6105与S9混合物的体外代谢中，鉴定出了几种代谢产物。在有机溶剂提取物中鉴定出了含有完整环氧基团的醇代谢产物3,4-环氧环己基甲醇。合成了这种代谢产物，并证明在有和没有S9混合物的情况下进行测定时，它对TA100具有致突变性。结果表明，在肝脏酶存在的情况下，Cyracure UVR-6105致突变性增加是由于诱变代谢产物3,4-环氧环己基甲醇的形成。
