Effects of clophen A50, 3-methylcholanthrene, pregnenolone-16 alpha-carbonitrile, and phenobarbital on the hepatic microsomal cytochrome P-450-dependent monooxygenase system in rainbow trout, Salmo gairdneri, of different age and sex
Förlin, L.
Toxicology and Applied Pharmacology 54(3): 420-430
1980
ISSN/ISBN: 0041-008X PMID: 6771886 Document Number: 159871
Four groups of rainbow trout (mature male and female, 12-year-old juvenile, and 112-year-old juvenile) were injected ip at Days 0 and 3 with 20 mg/kg 3-methylcholanthrene (3-MC), 500 mg/kg Clophen A50 (Cl A50), 40 mg/kg pregnenolone-16α-carbonitrile (PCN), respectively, and examined at Day 14. Further, one group of 112-year-old juvenile was injected ip daily with 80 mg/kg phenobarbital (PB) and examined at Day 14. Only 3-Mc and Cl A50 markedly elevated the total amount of cytochrome P-450 and the cytochrome P-450-dependent metabolism of paranitroanisole (PNA) and benzo (a)pyrene in the fish liver, whereas no such elevation were observed by Pcn or PB. In order to characterize the hepatic cytochrome P-450-dependent metabolism, the Michaelis-Menten kinetic constants of PNA-O-demethylase and the responses of the reactions to α-naphtoflavone, metyrapone, and Skf 525A, in vitro, were studied. These studies (A) showed Pcn to significantly elevate apparent Km of Pna metabolism, whereas no alterations of apparent Km were seen by 3-Mc or Cl A50, (B) indicated the hepatic reactions to be mediated by several species of cytochrome P-450, (C) indicated the formation of alternative form (s) of cytochrome P-450 species in 3-MC- or Cl A50-induced fish when compared to control fish, (D) showed 3-MC- and Cl A50-induced reactions to be similar in character. The presence of differences due to age and sex in the response to the inducers and in the response to the inhibitors, in vitro, is indicated.