Metabolism of 2-acetylaminofluorene by Shasta rainbow trout
Conference
·
OSTI ID:49466
- State University of New York, Buffalo, NY (United States)
- Univ. of Kentucky, Lexington, KY (United States)
In contrast to several mammalian species, Shasta strain rainbow trout (Oncorhynchus mykiss), is resistant to the hepatocarcinogenic effects of 2-acetylaminofluorene (AAF). In order to understand the mechanism underlying this resistance, the authors have investigated the in vitro metabolism of AAF by trout liver and examined the formation of AAF-DNA adducts in the liver of Shasta trout treated with AAF. The major AAF metabolites produced by trout liver microsomes were 7-hydroxy-AAF and 5-hydroxy-AAF which accounted for more than 95% of the total AAF metabolites. N-hydroxy-AAF was a minor metabolite representing about 1% of total AAF metabolites. The levels of N-hydroxy-AAF sulfotransferase and N-hydroxy-AAF acyltransferase, the cytosolic enzymes implicated in the metabolic activation of N-hydroxy-AAF to reactive intermediates capable of binding to cellular macromolecules were extremely low in trout liver. AAF exhibited a low degree of binding to the liver DNA of trout treated with 15 mg AAF/kg body wt. The total AAF-DNA adduct level reached a maximum 24 hours after treatment, persisted until 11 days and declined to nearly 20% of the maximum level after 18 days. N-deoxyguanosin-8-yl-2-aminofluorene was the major AAF-DNA adduct in the trout liver. The ability of trout liver to form relatively large amounts of detoxification products of AAF with little formation of activation products may partly explain the resistance of Shasta trout to AAF-induced hepatocarcinogenesis.
- OSTI ID:
- 49466
- Report Number(s):
- CONF-9410273--
- Country of Publication:
- United States
- Language:
- English
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