UTILITY OF DELAYED MUTATION TEST IN CHEMICAL MUTAGENESIS

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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.