Date of Award

2000

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

H. Wayne Taylor

Second Advisor

Jay C. Means

Abstract

Mechanisms of DNA alkylation and repair were investigated in 3 small fish species. Following aqueous exposure to either N-methyl- N'-nitro-N-nitrosoguanidine or ethyl methanesulfonate, the hepatic DNA from the western mosquitofish, Gambusia affinis, was analyzed for alkyl-DNA adducts via high performance liquid chromatography - mass spectrometry/mass spectrometry. Although potential tissue detection limits ranged from 14--101 fmoles of alkyl adducts/mg tissue, no alkyl-DNA adducts were detected in the exposed tissues. To assess the potential repair of alkyl-DNA adducts in 2 other small fish species, alkyltransferase activities within hepatic protein extracts of the Gulf killifish, Fundulus grandis, and Gambusia affinis were determined using an in vitro alkyl group transfer system. The alkyltransferase activities were detectable in both species, reaching a plateau with the removal of less than 31% of the available alkyl groups from DNA. Preincubation of the protein extracts with O6-benzylguanine failed to inhibit these alkyltransferase activities. Sheepshead minnows, Cyprinidon variegatus, were exposed to aqueous concentrations of N-methyl- N'-nitro-N-nitrosoguanidine, and then were examined histologically for evidence of neoplasia at 10 week intervals until 40 weeks post-exposure. No neoplasms were detected.

ISBN

9780599682214

Pages

123

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