Polycyclic aromatic hydrocarbon induction of cytochrome P-450-dependent mixed-function oxidases in marine fish

Abstract

Administration of 3-methylcholanthrene (3-MC) and related chemicals (1,2,3,4-dibenzanthracene, 7,12-dimethylbenzanthracene, and 5,6-benzoflavone) by ip or im injection to five species of marine fish resulted in increases in their hepatic microsomal mixed-function oxidase activities with benzo( a)pyrene, 7-ethoxycoumarin, and 7-ethoxyresorufin as substrates. Cytochrome P-450 content was increased in some treated fish. Sheepshead injected im with 3-MC showed the most marked induction of cytochrome P-450 content. In sheepshead, the Soret maximum of the CO-reduced difference spectrum changed from 450 nm in control to 448 or 449 nm in 3-MC-treated fish. The time course of 3-MC induction of benzo( a)pyrene hydroxylase activity in sheepshead changed with season (water temperature) and was not the same as the time course of induction of cytochrome P-450 content or 7-ethoxyresorufin O-deethylase activity. In summer (water temperature 26°C), benzo( a)pyrene hydroxylase activities in hepatic microsomes from 3-MC-treated sheepshead were maximum at 3 days and were back to control levels at 14 days after the dose, whereas in winter (water temperature 14°C) maximum activities were observed 8 days after dosing, but elevated activities were still observed 28 days after one ip dose. Epoxide hydrase and glutathione S-transferase activities were not induced by polycyclic aromatic hydrocarbons or 5,6-benzoflavone in the marine fish studied, at the doses tested.