BIOAVAILABILITY AND BIOTRANSFORMATION OF BENZO(A)PYRENE IN AN ISOLATED-PERFUSED IN-SITU CATFISH INTESTINAL PREPARATION

In the aquatic environment, diet is an important route of exposure for the common contaminant and procarcinogen benzo(a)pyrene (BaP). Dietar y organisms vary in their BaP content and in contaminated areas often contain other xenobiotics including cytochrome P4501A inducers. This s tudy examined the effect of dose and previous dietary exposure to the inducer beta-naphthoflavone (BNF) upon the intestinal metabolism of Ba P and the systemic bioavailability of BaP-derived products in catfish. BaP was administered at 2 and 20 mu M into in situ-isolated perfused intestines of control and BNF-pretreated catfish. The intestine formed an array of metabolites in all treatments including potentially hazar dous metabolites such as BaP-7,8 and 9,10 dihydrodiols and 6-methyl-Ba P. BNF treatment disproportionally increased the contribution of BaP-7 ,8 and 9,10 dihydrodiols relative to the contributions of other metabo lites. A greater percentage of metabolites was evident as conjugates i n 2 mu M controls, whereas a greater percentage of unconjugated metabo lites was evident for 20 mu M controls and BNF treatments of both dosa ges. BNF pretreatment and the higher 20 mu M BaP dosage resulted in gr eater bioavailability, with 2.6-5.5-fold and 3.0-6.3-fold increases in systemically available BaP products, respectively. Metabolites repres ented 10.2-23.1% of the increased bioavailability with BNF treatment, suggesting that mechanisms, in addition to induced metabolism, may be operative. These results indicate that intestinal bioavailability, lev el of biotransformation, and the metabolic profile of BaP-derived prod ucts entering the blood from the intestine may be altered by dose and dietary BNF pretreatment.