Heterogeneity of hepatic aryl hydrocarbon hydroxylase activity in feral winter flounder: relevance to carcinogenicity testing.
Hepatic microsomes from winter flounder (Pseudopleuronectes americanus), treated with polycyclic aromatic hydrocarbon (PAH) inducers, had elevated activities of benzo[alpha]pyrene hydroxylase (AHH) and 7-ethoxyresorufin deethylase (7-ERD). When electrophoresed, they showed a novel or enriched polypeptide species with a monomeric molecular weight of approximately 57,000. These results are consistent with inductive responses already well-characterized in several mammalian and fish species. However, when we studied the urinary clearance of 4-chlorobiphenyl in untreated flounder, wide variations (up to twentyfold) among fish were noted. Subsequent in vitro analysis of AHH and 7-ERD activities in liver demonstrated wide variations in these monooxygenase activities in flounder caught near Mount Desert Island, Maine. In some instances, AHH activities in these feral flounder were as high as those in PAH-induced fish. Based on the response of AHH activity to 7,8-benzoflavone (ANF) added in vitro, flounder could be divided into 2 groups; one had high hepatic AHH activity which was inhibited by ANF, the other had low AHH activity which was enhanced by ANF. Examination of a large number of winter flounder (greater than 400 total) over 4 experimental seasons demonstrated this variability of hepatic AHH activity to be a recurrent characteristic of the flounder population in waters around Mount Desert Island. The hepatic AHH activities did not correlate well with any physical parameter of the fish (e.g., liver, gonad or body weight, length, or sex) or the cytochrome P-450 content of the hepatic microsomes. Our attempt to evaluate the AHH activity (high vs. low) of individual fish in vivo by urinary clearance of antipyrine was unsuccessful, due to the excretion of large amounts of unchanged antipyrine through the gills. Similar studies were performed with another marine teleost, Fundulus heteroclitus. Of the approximately 200 Fundulus examined, almost all had AHH activity inhibited by ANF; in some experiments, hepatic 7-ERD activities were further increased after treatment with the potent PAH-type inducer 3,4,5,3',4',5'-hexachlorobiphenyl but only about twofold. Collectively, these data are consistent with PAH-type induction of the hepatic cytochrome P-450-dependent monooxygenase system in some feral marine teleosts (in winter flounder and Fundulus) from Maine by environmental contaminants or food constituents. It is not known whether these chemicals are of natural or anthropogenic origin. The variation in the response appears to be related to individual exposure level (dose) or sensitivity, or both.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System; D004247:DNA / Q000378:metabolism; D004790:Enzyme Induction; D005399:Fishes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology; D014116:Toxicology / Q000379:methods*
D001713:Biphenyl Compounds; D002273:Carcinogens; D011083:Polycyclic Compounds; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; C006983:4-chlorobiphenyl; D000983:Antipyrine