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P-NITROPHENOL AND GLUTATHIONE RESPONSE IN MEDAKA (ORYZIAS LATIPES) EXPOSED TO MX, A DRINKING WATER CARCINOGEN.
Citation:
Geter, D. R., J W. Fournie, M. Brouwer, A B. DeAngelo, AND W. E. Hawkins. P-NITROPHENOL AND GLUTATHIONE RESPONSE IN MEDAKA (ORYZIAS LATIPES) EXPOSED TO MX, A DRINKING WATER CARCINOGEN. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY - PART C: TOXICOLOGY & PHARMACOLOGY 134(3):353-364, (2002).
Description:
When chlorine is introduced into public drinking water for disinfection, it can react with organic compounds in surface waters to form toxic by-products such as 3-chloro-4- (dichloromethyl)-5-hydroxy-2[5H]-furanone (MX). We investigated the effect of exposure to MX on cytochrome P4502E1 (CYP2EI)-like activity and total g]utathione (GSH) in the liver of the small fish model, medaka (Oryzias latipes). The multi-site carcinogen methylazoxymeihanol-acetate (MAMAC) was the positive control compound. Both medaka liver microsome preparations and S-9 fractions catalyzed the hydroxylation of p-nitrophenol (PNP), suggesting CYP2E1-like activity in the medaka. Male medaka exposed for 96h to the CYP2E1 inducers ethanol and acetone under fasted conditions showed significant increases in PNP- hydroxylation activity. Furthermore, total reduced hepatic GSH was reduced in fish fasted for 96h, indicating that normal feeding is a factor in maintaining xenobiotic defenses. Exposure to MX and MAMAc induced significant increases in hepatic CYP2EI-like activity, however MX exposure did not alter hepatic GSH levels. These data strengthen the role of the medaka as a suitable species for examining cytochrome P450 and GSH detoxification processes and the role these systems play in chemical carcinogenesis.