Induction of cytochrome P-450 dependent reactions in the rat ventral prostate by β-naphthoflavone and 2,3,7,8-tetrachlorodibenzo- p-dioxin

Abstract

The purpose of this study was to characterize drug metabolism in the rat ventral prostate in untreated, β-naphthoflavone (BNF) or 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) treated animals. Intraperitoneally administered [ 3H] benzo[a] pyrene (BP) was recovered in about equal quantities in rat ventral prostate, lungs and testes. The relatively high uptake of [ 3H]BP in the ventral prostate might possibly be related to the occurence of a macromolecule in the gland binding TCDD and 3-methylcholanthrene (MC) with a relatively high affinity ( K d 1.5 and 5.0 μM, respectively). BNF, BP and MC competed with the TCDD binding site of the macromolecule. The prostatic cytochrome P-450 dependent microsomal enzyme activities aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase are very low in untreated animals (about 1 pmol/min/mg of microsomal protein). BNF- or TCDD treatment of the animals induced these activities about 500-fold, whereas aminopyrine N-demethylase was enhanced to a smaller degree. Maximal enzyme activities of AHH and 7-ethoxyresorufin O-deethylase were obtained 24 h after a single intraperitoneal injection of BNF and the activities decayed relatively rapidly after this peak. The magnitude of enzyme induction was much higher in the prostate than in the liver. Mutagenic BP metabolites were formed in vitro by induced prostatic microsomes as revealed by HPLC analysis. The activity of NADPH-cytochrome c reductase was 35 pmol/min/mg and was not changed by BNF- or TCDD treatment.