Cytochrome P4501A induction and testosterone hydroxylation in cultured hepatocytes of four fish species.
Primary hepatocytes of the rainbow trout (Oncorhynchus mykiss), flounder (Platychthis flesus), dab (Limanda limanda) and lemon sole (Microstomus kitt) were exposed to 3,3'4,4'5 pentachlorobiphenyl (PCB 126) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for two days. This resulted in a dose-dependent induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O-deethylase (EROD), or methoxyresorufin O-deethylase (MROD) activity. In all species, a linear relationship was observed between EROD and MROD activities, suggesting that the same CYP1A enzyme metabolizes the two alkoxy-resorufin substrates. Exposures of hepatocytes of flounder or dab to TCDD, resulted in a 59-fold and 8.2-fold induction of EROD activity, respectively. This did not concur with a change in the in vitro testosterone hydroxylation profiles of both species. These and other in vitro data indicate that TCDD exposure does not influence monooxygenase activities involved in testosterone hydroxylation. Furthermore, CYP1A is of minor importance for testosterone hydroxylation in these fish species.
Smeets
Jean M W
JM
Institute for Risk Assessment Sciences, University of Utrecht, The Netherlands.
Wamsteker
Jasper
J
Roth
Bart
B
Everaarts
Jan
J
van den Berg
Martin
M
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000494:pharmacology; D004785:Environmental Pollutants / Q000009:adverse effects*; D004790:Enzyme Induction; D004965:Estrogen Antagonists / Q000009:adverse effects*; D005399:Fishes / Q000502:physiology*; D022781:Hepatocytes / Q000201:enzymology; D006900:Hydroxylation; D008297:Male; D010088:Oxidoreductases / Q000096:biosynthesis / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects*; D013739:Testosterone / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000009:adverse effects*
D004785:Environmental Pollutants; D004965:Estrogen Antagonists; D000072317:Polychlorinated Dibenzodioxins; D014874:Water Pollutants, Chemical; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl