UTILITY OF DELAYED MUTATION TEST IN CHEMICAL MUTAGENESIS

这是一项学术研究增强奖(AREA)的申请，旨在为科学家创造一个研究机会，否则他们不太可能参与NIH计划。这项研究包括测试化学物质的致突变性，以预测果蝇的致癌性。因此，该项目与健康有关。虽然果蝇被成功地用来预测化学物质的致癌性，但在这个系统中，一些强大的致癌物是阴性的。然而，果蝇表面上的不敏感可能是因为选择了不适当的终点来测试特定的可疑致癌物质。因此，一些对最敏感的性连锁隐性致死测试没有反应的强致癌物质将被测试其诱导延迟突变和复制不稳定性的能力。这两种现象都是由单链损伤引起的，这是化学品的一个特征。果蝇文献中有证据表明，在传统的性别连锁隐性致死试验中发现阴性的化合物确实会导致数量不多的嵌合体突变。因此，有可能通过测试它们诱发嵌合突变和复制不稳定性的能力来识别明显为阴性的致癌物的遗传毒性。突变检测实验将使用F2检测的正交基方法进行。这些实验将继续进行下一代(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.