UTILITY OF DELAYED MUTATION TEST IN CHEMICAL MUTAGENESIS

这是学术研究增强奖（AREA）的申请，旨在为科学家创造一个研究机会，否则不太可能参加NIH计划。 该研究涉及使用果蝇测试化学品的致突变性以预测致癌性。 因此，该项目与健康有关。 虽然果蝇被成功地用于预测化学物质的致癌性，但一些强致癌物在该系统中是阴性的。 然而，果蝇明显的不敏感性可能是由于选择了不适当的终点来测试特定的可疑致癌物。 因此，将对一些对最敏感的性连锁隐性致死试验无反应的强效致癌物进行诱导延迟突变和复制不稳定性的能力试验。 这两种现象都是由于单链损伤的诱导，这是化学品的一个特征。 果蝇文献中有证据表明，在常规性连锁隐性致死试验中发现阴性的化合物确实诱导了不显著数量的嵌合突变。 因此，可以通过检测其诱导嵌合突变和复制不稳定性的能力来识别明显阴性致癌物的遗传毒性。 将使用用于F2检测的orthodos Basc方法进行突变检测实验。这些实验将继续进行一个世代（F3），以检测延迟突变。

This is an application for Academic Research enhancement Award (AREA) which is intended to create a research opportunity for scientists otherwise unlikely to participate in NIH program. The research involves testing of chemicals for their mutagenicity to predict the carcinogenicity using Drosophila. The project therefore is health related. Although Drosophila is being used successfully to predict carcinogenicity of chemicals, some potent carcinogens were negative in this system. The apparent insensitivity of Drosophila may, however, be due to an inappropriate end point chosen to test a particular suspect carcinogen. Therefore, some potent carcinogens, which did not respond to the most sensitive sex-linked recessive lethal test, will be tested for their capacity to induce delayed mutations and replicating instabilities. Both these phenomena result from the induction of single strand damage, which is a characteristic of chemicals. There is evidence in the Drosophila literature suggesting that compounds found negative in conventional sex- linked recessive lethal test do indeed induce insignificant numbers of mosaic mutations. Therefore, it is possible that the genotoxicity of apparently negative carcinogens may be discerned by testing their ability to induce mosaic mutations and replicating instabilities. Mutation detection experiments will be performed using the orthodos Basc method for F2 detection. These experiments will be continued for one more generation (F3) to detect the delayed mutation.