This proposal is for a series of collaborative studies involving the Epidemiology Unit and the Chemical Carcinogenesis Unit of the Unviersity of Southern California Comprehensive Cancer Center and the Department of Nutrition and Food Science at the Massachusetts Institute of Technology. The overall objective of this research is to elucidate the etiologic relationship between ingestion of Cantonese-style salted fish and the development of nasopharyngeal carcinoma (NPC) in southern Chinese as suggested by the findings of our recent case-control study in Hong Kong. We will conduct a similar case-control study in Guangzhou, People's Republic of China to confirm the findings in Hong Kong. Cases will be histologically confirmed incident cases of NPC under age 50 at the time of diagnosis. Controls will be age- (within 5 years) and sex-matched neighborhood controls. We plan to complete 300 case-control pair interviews. We will conduct a controlled animal experiment in which 148 inbred Wistar-Kyoto rats will be fed a diet of powdered salted fish and rat chow mixture to determine whether Cantonese-style salted fish is carcinogenic in this animal model. We will conduct laboratory studies to determine the ability of salted fish extracts in causing mutation to ouabain and to 8-azaguanine resistance and in inducing neoplastic transformation in mammalian cells. We will conduct laboratory studies to isolate and identify the compounds in salted fish extracts which form bacterial mutagens following nitrosation under simulated gastric conditions. Compounds that have been identified as mutagenic in the facterial assays will be retested in mammalian cell assays including cultured diploid human foreskin fibroblasts to characterixe their ability to cause genotoxicity in human cells.
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