Date of Award

1997

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Veterinary Medical Sciences - Pathobiological Sciences

First Advisor

Martin E. Hugh-Jones

Abstract

The main goal of the study was to provide the basic technical frame work for the use of native fish species as environmental sentinels for potential human exposure to genotoxic agents in general and to 1,2-dichloroethane (ethylene dichloride) in particular. First, LC/MS/ESI/ID and LC/MS/MS/ESI/ID methods for detection and quantification of S- (2-(N$\sp7$-guanyl)ethyl) glutathione DNA adduct from biological samples was developed. The methods were tested by exposing groups of rats with three dose levels of 1,2-dibromoethane. They allowed detection of $\sim$1 adduct in 10$\sp7$ bases. Second, the formation and persistence of DNA adduct in channel catfish (Ictalurus punctatus) from 1,2-dichloroethane exposure was studied under controlled laboratory conditions. DNA adducts formed rapidly, within two hours of exposure. The peak of the DNA adduct (265 pmol/mg DNA) formation was 4 hours post-exposure with a half-life of 2-5 days. However, the DNA adduct was detectable three weeks after end of exposure. Third, a dose-response relationship, with the dose in ppm and response as DNA adducts' frequency per mg DNA, was established. The biological response was linear up to 200 ppm and appeared to level off thereafter. Finally, the effect of depletion of glutathione on DNA adduct formation was studied. DNA adducts were not detected in fish pre-treated with diethylmaleate (DEM) (detection limit, $\sim$10 fmol on column). The results from this study provide the first evidence for the potential use of channel catfish as sentinel animals for 1,2-dichloroethane environmental contamination. Furthermore, the hepatic DNA adduct in channel catfish may serve as a dosimeter of exposure and thus may be used to differentiate areas of high pollution.

ISBN

9780591723922

Pages

87

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