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Development of the Zebra Danio Model: Carcinogenesis and Gene Transfer Studies

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Final rept. 12 Aug 91-11 Aug 96

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Zebrafish Brachydanio rerio were evaluated as a small fish model for environmental carcinogenesis monitoring. Criteria used for evaluation included 1 sensitivity to dose response exposures of 6 known carcinogens by 4 routes of exposure, 2 histopathologic evaluation of the resulting lesions and comparison with responses in other species, 3 response to promoters of neoplasia, 4 ability to conduct carcinogen metabolism studies to understand mechanisms of action, 5 determining the role of oncogenes in zebrafish carcinogenesis, and 6 success in developing transgenics that would increase the species usefulness as a carcinogen monitoring model. Findings were 1 zebrafish did respond to known carcinogens with variable but overall acceptable sensitivity, 2 the histopathology of their responses was similar to that observed in other small fish species, 3 they did not respond well in limited promotional studies, 4 metabolism studies were very difficult due to small fish and organ size and results did not always support observed tumor responses, 5 ras and p53 genes were sequenced but lack of grossly observable tumors prevented the determination of mutations in these genes, and 6 although progress was made, the production of transgenic fish was not achieved. Although none of these results would disqualify zebrafish as environmental monitors, their strict requirement for tropical or subtropical water temperatures would make them completely unsuitable for temperate water use.

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  • Genetic Engineering and Molecular Biology
  • Biology
  • Medicine and Medical Research

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