MUTAGENIC ACTIVITY OF ANTI-HERPES DRUGS

抗疱疹药物的诱变活性

• 批准号: 3183764
• 负责人: LEWIS I PIZER
• 金额: $ 4.81万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3183764
• 关键词: Alphaherpesvirinae; Herpesviridae; antiviral agents; chemical carcinogen; drug adverse effect; drug resistance; nucleoside analog; nucleotides; thymidine kinase

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.

我们希望开发和测试程序来测量 用于治疗人类疱疹病毒感染的化学治疗剂。 的 最有效的抗病毒药物对单纯疱疹病毒感染 是发挥其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 已知这些类似物具有致突变性。 建议的目标 研究的目的是构建表达 HSV胸苷激酶，并通过使用这些细胞确定是否抗疱疹 药物导致明确的营养和耐药性标志物发生 进一步突变。 上面概述的策略类似于艾姆斯描述的策略，其中 具有确定突变的细菌被用于检测化学致癌物。