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2005 Georgia Veterinary Scholars

Georgia Veterinary Scholar	Faculty Mentor
Owen Fink University of Georgia Class of 2008	Dr. Richard Winn

Ultraviolet-B Radiation-Induced Mutagenesis in the Transgenic Fish and Mouse.

Owen Fink*, Richard Winn. Aquatic Biotechnology and Environmental Laboratory, Warnell School of Forestry Resources, University of Georgia

Solar ultraviolet-B radiation (UVB) induces genetic damage in DNA, and is a major cause of melanoma and non-melanoma skin cancers. We examined UVB-induced mutations in transgenic fish and mice models. The main aims of the study are 1) to examine the fundamental mechanisms of genetic damage directly at the level of the DNA, and 2) to evaluate the extent to which fish may be used as surrogates for rodents in future UVB mutagenesis studies. To study mutations in endogenous genes poses several practical problems. First, the sequence of the gene must be well known so that a mutant can be distinguished from a non-mutant. Secondly, the low frequency of mutations means that the gene must be recovered and analyzed efficiently and in large numbers. Finally, genetic variation between species can make cross-species comparisons difficult. To overcome these challenges we used transgenic animals in our study. A transgenic animal has DNA that has been modified through the insertion of foreign genes. Specifically, we used transgenic fish and mice that carry a mutation reporter gene that allows rapid and efficient mutation analysis. After exposing the animal to a mutagen, the reporter gene is recovered in large numbers and analyzed for mutations. This analysis yields information about the DNA-level effects of the mutagen. Using the identical reporter gene in both the fish and mice allows direct cross-species comparison. To examine UVB-induced mutagenesis, we exposed transgenic fish and mice, each carrying the cII reporter gene, to varying doses of UVB exposure from a calibrated lamp. Mice were depilated prior to exposure. After a two week period to allow mutations to manifest, all animals were euthanized and skin samples were taken from the exposed area. DNA was isolated and the reporter gene was recovered and analyzed. The reporter gene mutation frequency in exposed and unexposed animals was compared to determine the relative induction of mutations. This study will provide new data clarifying the role of fish as alternative non-mammalian models of human disease. Since many fundamental molecular processes are conserved across the two species, we expect results to show similar UVB mutation induction. Information about both the similarities and the differences between the fish and mice responses will be valuable for future UVB mutagenesis studies.