Induction of cytochrome P-448 activity as exemplified by the O-deethylation of ethoxyresorufin. Effects of dose, sex, tissue and animal species.

The effects of tissue, sex, animal species and dose on the induction of cytochrome P-448 activity by various inducing agents were investigated using O-ethoxyresorufin as a model substrate. The liver was by far more effective in catalysing the O-deethylation of ethoxyresorufin (EROD) than the lung and kidney. The extent of induction was also highest in the liver, with the exception of benzo(a)pyrene and 3-methylcholanthrene where inducibility was more pronounced in the kidney. The benzo(a)pyrene-induced hepatic EROD activity in the rat decayed to reach control levels four days after a single administration. Rat hepatic EROD activity was induced in both sexes but tended to be higher in the male. Marked species differences in the inducibility of hepatic EROD activity by various chemicals was observed, the rat being always more responsive when compared to the hamster or mouse. The induction of rat hepatic EROD activity by benzo(a)pyrene, 2-acetylaminofluorene and safrole was dose-dependent, maximum induction being achieved with single doses of 5, 2 and 5 mg/kg, respectively.