MUTAGENIC ACTIVITY OF ANTI-HERPES DRUGS

我们希望开发和测试程序来测量的诱变活性 用于治疗人类疱疹病毒感染的化疗药物。这个 治疗单纯疱疹病毒感染最有效的抗病毒药物 是具有选择性毒性的核苷类似物，因为它们 被病毒酶，胸苷激酶转化为核苷酸。一些人 这些类似物中已知有致突变性。建议的目标是 这项研究是为了构建培养的哺乳动物细胞系，表达 HSV胸苷激酶和通过使用这些细胞来确定是否有抗疱疹作用 药物导致明确定义的营养和耐药标志物经历 进一步的突变。 上面概述的策略类似于Ames所描述的策略 具有明确突变的细菌被用来检测化学致癌物。

We wish to develop and test procedures to measure the mutagenic activity of chemotherapeutic agents used to treat human herpes virus infections. The most effective anti-viral agents against herpes simplex virus infections are nucleoside analogues that exert their selective toxicity because they are converted to nucleotides by the viral enzyme, thymidine kinase. Some of these analogues are known to be mutagenic. The goal of the proposed research is to construct lines of cultured mammalian cells that express the HSV thymidine kinase and by use of these cells determine if anti-herpetic drugs cause well-defined nutritional and drug resistance markers to undergo further mutation. The strategy outlined above is analogous to that described by Ames in which bacteria with defined mutations are used to detect chemical carcinogens.