Metabolism of benzo[a]pyrene in rat prostate glands following 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure

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Abstract
The present study was undertaken to determine, using h.p.l.c., both the rate and pattern of benzo[a]pyrene (BP) metabolism in monooxygenase(s)-induced and non-induced prostate glands of adult Sprague Dawley rats (CD-strain). H.p.l.c. analysis showed that for non-induced prostate glands, the initial synthetic rates of dihydrodiols, quinones and phenols in the organic extractable phase were 0.16, 0.18 and 0.16 pmol/min/mg protein, while for the total BP metabolites in the aqueous phase it was 5.4 pmol/min/mg protein. Therefore, BP metabolism in the non-induced prostate gland is extremely low, with the total of BP metabolites in the aqueous phase being approximately 11 times greater than the total of BP metabolites in the organic phase. In contrast, the rates of phenol, quinone and dihydrodiol synthesis in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced prostate glands were 45.9, 34.5 and 6.0 pmol/min/mg protein, respectively, and are thus significantly increased by 290, 192 and 38 times, respectively over control rates. At the highest TCDD dose (10 μg/kg body weight), the synthetic rates for phenols and quinones increased by 200–300-fold and for the diols about 35-fold over controls. The rate of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene synthesis was greater than 4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene or 9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene synthesis. Furthermore, the ratios of the total BP metabolites in the organic phase to those in the aqueous phase of control and TCDD-induced were 0.09 and 3.3, respectively. Thus, it is clear that one of the major effects of TCDD in rat prostate glands is to significantly increase organic-soluble BP metabolites over water-soluble BP metabolites. These experiments also demonstrated that the specific aryl hydrocarbon hydroxylase (AHH), epoxide hydrotase (EH) and glutathione transferase (GSH-T) activities at the maximum substrate concentrations of BP and 4,5-benzo[a]pyrene 4,5-oxide in non-induced prostate glands of CD-rats are 0.25, 50, 12,500 pmol/min/mg protein, respectively. Thus, it is clearly shown that specific prostatic AHH activity is extremely low when compared to EH or GSH-T activity, which are 200 or 50,000 times greater than AHH activity, respectively. However, TCDD treatment significantly increased the specific prostalic AHH activity (200 times), as well as the cytochrome P-446 species (7 times), while specific EH and GSH-T activities were not altered.