Superfund Research Program

Bioavailability of Chlorinated Compounds

Project Leader: Margaret O. James
Grant Number: P42ES007375
Funding Period: 1995-2006

Project-Specific Links

Final Progress Reports

Year:   1999 

The objectives of project 6 are to further the understanding of factors affecting the intestinal bioavailability of chlorinated compounds. In the past year, it was shown that pretreatment of the fish with 3,3',4,4'-tetrachlorobiphenyl (TCB) prior to infusion of [14C]-TCB to an in situ channel catfish intestinal preparation led to reduced binding of [14C]-TCB to intestinal mucosal cytosol, compared with fish that were not pretreated with TCB in the diet. Treatment of fish with the aryl-hydrocarbon receptor agonist, beta-naphthoflavone (BNF), did not alter the cytosolic protein binding of [14C]-TCB, suggesting the effect was not aryl-hydrocarbon-receptor-related. Since TCB but not BNF pretreatment reduced the transfer of the [14C]-TCB to blood, it was thought that this cytosolic binding may be important in determining the extent of transfer of TCB from intestinal mucosal cells to blood. The cytosolic binding persisted through dialysis, but not through SDS-PAGE of the cytosolic proteins, suggesting high affinity, but reversible binding. Other studies investigated the P-glycoprotein transporter in catfish intestine. Image analysis of immunohistochemical studies suggest that TCB, BNF and benzo (a) pyrene induce an immunoreactive P-glycoprotein in the mucosal epithelia along the intestinal brush border. This agreed with previous studies showing inducible transport activity consistent with P-glycoprotein. Monoclonal C-219 antibody detection methodologies using Western blotting procedures with harvested mucosa gave less definitive results, perhaps due to cross-reactivity of C-219 with myosin components present in mucosa and perhaps due to inherent sensitivity problems for detection of low levels of protein by Western blot.