In vivo binding of 2,3,6,2',3',6'-hexachlorobiphenyl and 2,4,5,2',4',5'-hexachlorobiphenyl to mouse liver macromolecules.
The role of metabolic activation in the binding of polychlorinated biphenyls (PCBs) to cellular macromolecules was investigated in vivo by comparing the relative binding of 2,4,5,2',4',5'-[U-14C]hexachlorobiphenyl (2,4,5), a slowly metabolized PCB, with that of 2,3,6,2',3',6'[U-14C]hexachlorobiphenyl (2,3,6), a rapidly metabolized PCB, and the appropriate controls. Each hexachlorobiphenyl was administered to mice, orally for 5 days (7.28 mg/kg/day). Following the dosing schedule, animals were killed at 1, 5 and 8 days. The concentration of each PCB was determined in liver, muscle and kidney and in purified macromolecules isolated from those tissues. The concentration of 2,4,5 was consistently higher than the concentration of 2,3,6 in all tissues studied. However, the amount of 2,3,6 bound to the purified macromolecules was consistently at least one order of magnitude greater than that of 2,4,5. The greatest binding was observed in RNA followed by protein and DNA, respectively. The purity of the macromolecules and the presence of PCB-derived radioactivity at the monomer level were confirmed. This is the first report of 14C-labeled PCB being bound to purified RNA, DNA, and proteins isolated from the tissues of animals treated in vivo. The binding is thought to be covalent and to be the result of metabolic activation.
D000818:Animals; D004247:DNA / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009928:Organ Specificity; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D013329:Structure-Activity Relationship
D011506:Proteins; D012313:RNA; D004247:DNA; D011078:Polychlorinated Biphenyls; C010498:2,3,6,2',3',6'-hexachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl