title: p-Nitrophenol and glutathione response in medaka (Oryzias latipes) exposed to MX, a drinking water carcinogen.
abstract: 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 P450 2E1 (CYP2E1)-like activity and total glutathione (GSH) in the liver of the small fish model, medaka (Oryzias latipes). The multi-site carcinogen methylazoxymethanol 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 96 h 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 96 h, indicating that normal feeding is a factor in maintaining xenobiotic defenses. Exposure to MX and MAMAc induced significant increases in hepatic CYP2E1-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.
authors.affiliation: Department of Coastal Sciences, Gulf Coast Research Laboratory, The University of Southern Mississippi, Ocean Springs, MS 39564, USA. geter.david@epa.gov
authors.forename: David R
authors.initials: DR
authors.lastname: Geter
authors.forename: John W
authors.initials: JW
authors.lastname: Fournie
authors.forename: Marius H
authors.initials: MH
authors.lastname: Brouwer
authors.forename: Anthony B
authors.initials: AB
authors.lastname: DeAngelo
authors.forename: William E
authors.initials: WE
authors.lastname: Hawkins
mesh_terms: D000096:Acetone / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005215:Fasting; D005260:Female; D005663:Furans / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D009596:Nitrophenols / Q000378:metabolism*; D009990:Oryzias / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply
chemical_list: D002273:Carcinogens; D005663:Furans; D009596:Nitrophenols; D014874:Water Pollutants, Chemical; D000096:Acetone; D000431:Ethanol; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D019392:Cytochrome P-450 CYP2E1; D005978:Glutathione; C024836:4-nitrophenol