Interaction of 3,4,3',4'-tetrachlorobiphenyl metabolites formed by cytochrome P-450 in vitro with rat erythrocytes.
Incubation of 14C-labeled 3,4,3',4'-tetrachlorobiphenyl (TCB) with a reconstituted monooxygenase system containing cytochrome P-450 isolated from 3-methylcholanthrene (MC)-treated rats caused an increase in incorporation of radioactivity to added rat erythrocytes and resulted in covalent binding of reactive metabolites to hemoglobin. Both increases in incorporation and covalent binding to the proteins were dependent on incubation time and required cytochrome P-450-linked monooxygenase activity. In the absence of erythrocytes, the reactive TCB metabolites bound to cytochrome P-450, NADPH-cytochrome P-450 reductase, and high-molecular weight aggregates, as determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, whereas inclusion of the cells in the reaction mixture caused marked alkylation of hemoglobin and a decrease in binding to the electron transfer proteins. Several metabolites other than protein-bound metabolites were detected by thin-layer chromatography; some were found to be incorporated into the erythrocytes while others were not. These results suggest that several TCB metabolites formed by cytochrome P-450 can interact with rat erythrocytes in vitro, and that these interactions may be responsible for the persistence of TCB metabolites in blood observed in vivo.
D000818:Animals; D002855:Chromatography, Thin Layer; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats
D006454:Hemoglobins; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl