Binding of polychlorinated biphenyls/metabolites to hemoglobin.
Polychlorinated biphenyls (PCBs) may form reactive electrophiles that can bind covalently to hemoglobin in vivo. Female C57/BL6 mice, pretreated with phenobarbital and P-naphthoflavone, were injected with either radiolabeled 4-chlorobiphenyl, 3,3',4.4'-tetrachlorobiphenyl, benzo[a]pyrene (B[a]P) or the corresponding non-labeled 4-chlorobiphenyl, 3.3',4.4'-tetrachlorobiphenyl, B[a]P or vehicle. Blood was collected at different time points. At 24 h a greater presence of 4-chlorobiphenyl and 3,3',4.4'-tetrachlorobiphenyl in the plasma, compared with the erythrocytes, was observed. For all three treatment groups the radioactivity in the hemolysate was found to be greater than the vehicle-treated group, except at 2 h after dosing, suggesting an association with hemoglobin. Covalent binding with globin was 10-fold greater for 4-chlorobiphenyl-treated animals compared with 3,3',4,4'-tetrachlorobiphenyl-treated animals. Liquid chromatography-mass spectral analysis of globin was used to identify adducts. Our preliminary data show an increase in mass corresponding to adducts of oxidized metabolites of PCBs. Detection of adducts of PCBs with hemoglobin could provide a valuable tool to evaluate acute exposure of a population.
Tampal
Nilufer
N
Graduate Center for Toxicology, Chandler Medical Center, University of Kentucky, 306 Health Sciences Research Building, Lexington, KY 40536-0305, USA.
Myers
Steven
S
Robertson
Larry W
LW
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D001713:Biphenyl Compounds / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005914:Globins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000097:blood*; D019324:beta-Naphthoflavone / Q000494:pharmacology
D015415:Biomarkers; D001713:Biphenyl Compounds; D006454:Hemoglobins; D001564:Benzo(a)pyrene; D019324:beta-Naphthoflavone; D005914:Globins; D011078:Polychlorinated Biphenyls; C006983:4-chlorobiphenyl; C028451:3,4,3',4'-tetrachlorobiphenyl; D010634:Phenobarbital