Marquardt H, Westendorf J, De Clercq E, Marquardt H
Carcinogenesis. 1985 Aug;6(8):1207-9. doi: 10.1093/carcin/6.8.1207.
(E)-5-(2-bromovinyl)-2'-deoxyuridine (BDVU), one of the most potent and selective anti-herpes agents described to date, and its close congeners (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU) and (E)-5-(2-bromovinyl)uracil (BVU), as well as the reference compounds 5-iodo-2'-deoxyuridine (IDU) and 5-trifluoro-2'-deoxythymidine (TFT) were examined for their genotoxic potential. With the exception of a weak activity of TFT in the newly developed strain TA 102, none of the compounds was active in a bacterial cell mutagenesis (Salmonella/microsome) assay. Nor did they induce DNA repair (unscheduled DNA synthesis) in primary rat hepatocytes. In a mammalian cell mutagenesis assay using V79 Chinese hamster cells, the reference compounds IDU and TFT proved highly cytotoxic and mutagenic, whereas BVDU, BVaraU and BVU were neither cytotoxic nor mutagenic.
(E)-5-(2-溴乙烯基)-2'-脱氧尿苷(BDVU)是迄今为止所描述的最有效和最具选择性的抗疱疹药物之一,及其类似物(E)-5-(2-溴乙烯基)-1-β-D-阿拉伯呋喃糖基尿嘧啶(BVaraU)和(E)-5-(2-溴乙烯基)尿嘧啶(BVU),以及参考化合物5-碘-2'-脱氧尿苷(IDU)和5-三氟-2'-脱氧胸苷(TFT),对它们的遗传毒性潜力进行了检测。除了TFT在新开发的TA 102菌株中具有微弱活性外,这些化合物在细菌细胞诱变(沙门氏菌/微粒体)试验中均无活性。它们也未在原代大鼠肝细胞中诱导DNA修复(非程序性DNA合成)。在使用V79中国仓鼠细胞的哺乳动物细胞诱变试验中,参考化合物IDU和TFT具有高度细胞毒性和诱变性,而BDVU、BVaraU和BVU既无细胞毒性也无诱变性。