Effect of micelle fatty acid composition and 3,4,3 ',4 '-tetrachlorobiphenyl (TCB) exposure on intestinal [C-14]-TCB bioavailability and biotransformation in channel catfish in situ preparations

Polychlorinated biphenyls are transferred in the diet along aquatic food ch ains. This study investigated the effect of dietary micelle composition and 3,4,3',4'-tetrachlorobiphenyl (TCB) exposure upon the subsequent systemic bioavailability and intestinal metabolism of [C-14]-TCB in a catfish in sit u intestinal preparation. Initial in vitro experiments examined the solubil ity of [C-14]-TCB in micelles of varying fatty acid composition. Micelles c omposed of single fatty acids demonstrated greater [C-14]-TCB solubility wi th those fatty acids of longer chain length. Similarly, micelles of the lon g-chain fatty acid, linoleic acid, solubilized more [C-14]-TCB than mixed m icelles formulated from equal amounts of myristic (14:0), palmitic (16:0), stearic (18:0), or linoleic (18:2) acids. Systemic bioavailability of [C-14 ]-TCB (60 mu M) from an in situ perfused intestinal preparation was 2.2-fol d greater when delivered to the intestine in linoleic acid micelles as comp ared to the mixed micelle preparation. Catfish exposed in vivo to either 0. 5 or 5.0 mg TCB/kg feed for 10 days resulted in a 45 to 47% decrease in the subsequent systemic bioavailability of [C-14]-TCB in the in situ intestina l preparation. Total intestinal cytochrome P450 content was not significant ly affected by TCB preexposure. Immunodetectable CYP1A was found only in th e 5.0 mg TCB/kg diet treatment. Corresponding intestinal aryl hydrocarbon h ydroxylase (AHH) activities were 2.46 +/- 1.16, 2.43 +/- 1.58, and 11.35 +/ - 10.25 pmol/min/mg protein for the control, 0.5, and 5 mg TCB/kg diet grou ps, respectively. [C-14]-TCB in the in situ preparation was metabolized to only a small degree upon a single pass through the intestinal mucosa of the catfish. High variability and low rates of metabolism precluded the associ ation of the magnitude of metabolism with dietary TCB pretreatment. Analysi s of tissue sample extracts demonstrated 4 minor peaks, 3 of which were ten tatively identified by co-elution with standards as 2-OH-3,4,3',4'-TCB, 4-O H-3,5,3',4'-TCB, and 5-OH-3,4,3',4'-TCB. A fourth remains unidentified. His tological changes in the intestine such as thinning of the submucosa and in creased numbers of goblet cells were evident at the 5.0 mg TCB/kg diet dose . These results suggest that TCB intestinal bioavailability may be linked t o micelle composition as well as TCB exposure history. Furthermore, single pass intestinal metabolism appears to be a minor contributor to the biotran sformational modification of dietary TCB.