Glutathione S-transferase in intestine, liver and hepatic lesions of mummichog (Fundulus heteroclitus) from a creosote-contaminated environment

Abstract

Cytosolic glutathione S-transferase (GSH transferase) activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was elevated approximately three to four-fold in intestine and liver of mummichog (Fundulus heteroclitus) collected from a creosote-contaminated site in the Elizabeth River, Virginia. Intestinal GSH transferase activity at the most heavily contaminated site, at a moderately contaminated site and at a relatively clean site averaged 3.64, 2.83 and 1.11µmoles/min/mg respectively, while values for liver at these sites averaged 2.84, 1.75 and 0.93µmoles/min/mg. In addition, densitometric tracings of sodium dodecylsulfate-polyacrylamide gels of intestine and liver cytosol revealed a similar trend in the staining intensity of a 25.8 kD protein band, which lies within the molecular weight range of GSH transferase subunits. Activity in putative preneoplastic and neoplastic hepatic lesions of fish collected from the creosote-contaminated site was not significantly different from that of adjacent normal tissue. In the laboratory, dietary betanaphthoflavone (ßNF) treatment resulted in a three-fold increase in intestinal GSH transferase. Hepatic GSH transferase activity in the same fish was not affected by dietary ßNF although hepatic monooxygenase activity, measured as ethoxyresorufin O-deethylase (EROD), was. The results of this study indicate a response of the intestinal detoxification system to environmental contaminants and supports previous studies on the importance of intestinal metabolism of foreign compounds. Further, our results indicate the trend towards elevated GSH transferase in liver of feral fish could not be attributed to a cancerous disease state in these fish but indicates chemical induction in this organ as well.

Intrastrain and interstrain variability in biotransformation enzyme activities of rainbow trout (Oncorhynchus mykiss)

“…Treatment of several fish species by intraperitoneal injection of PAHs produced a twofold induction of GST activity (George and Young 1988;Van Veld et al 1991). When rainbow trout were intraperitoneally injected with BNF, a twofold and 2.5-fold (Goksøyr et al 1987) induction of hepatic GST activity was found.…”

Altered expression of the xenobiotic transporter P-glycoprotein in liver and liver tumours of mummichog Fundulus heteroclitus from a creosote-contaminated environment

“…These alterations include suppression of enzymes involved in both xenobiotic activation and production of reactive oxygen species (e.g. CYP1A) and elevation of bene cial phase II detoxif ying enzymes such as G STs (van Veld et al 1991, Armknecht et al 1998). Overall, the pattern of expression of mummichog proteins and enzymes studied thus far (CYP1A, GST, Pgp) is similar to that believed to contribute to xenobiotic resistance in the early stages of carcinogen esis (Buchman et al 1985, Room i et al 1985, Fairchild et al 198 7, Farber 1991.…”

Up-regulation of hepatic ABCC2, ABCG2, CYP1A1 and GST in multixenobiotic-resistant killifish (Fundulus heteroclitus) from the Sydney Tar Ponds, Nova Scotia, Canada

“…A correlation between GST activity and PAH burden has previously been reported in mussels (Gowland et al, 2002), and killifish collected in the PAH-contaminated Elizabeth River had elevated GST activity (Van Veld et al, 1991;Armknecht et al, 1998). Heavy metals or their metabolites are also inducers of hepatic GST as reported for arsenic-exposed rat hepatocytes (Liu et al, 2001).…”