Metabolism of polychlorinated biphenyls by Gunn rats: identification and serum retention of catechol metabolites.
The tissue distributions of persistent metabolites of polychlorinated biphenyls (PCBs) in Wistar rats and homozygous uridine diphosphate glucuronosyltransferase (UGT) deficient Gunn rats exposed to 2,4,5,2',5'-pentachlorobiphenyl (CB101) and the commercial PCB mixture, Kanechlor-500 (KC500), were investigated. After exposure to CB101, four hydroxy and two methylsulfonyl (MeSO2) metabolites were detected in liver, lung, kidney, blood, and adipose tissues. One was identified as 3',4'-(OH)2-2,4,5,2',5'-pentaCB, which was retained selectively in the serum of Gunn rats. Comparative analysis of the metabolite profiles in both rat strains after exposure to KC500 showed higher formation ratios of several dihydroxy PCB metabolites in the liver of Gunn rats; major metabolites are the catechols from 2,5,3',4'-tetraCB, CB101, 2,3,6,3',4'-pentaCB, and 2,3,6,2',4',5'-pentaCB. Thus, Gunn rats effectively metabolized PCBs with 2,5- or 2,5,6-chlorine substitution to the 3,4-catechol, but less formed MeSO2 metabolites in the liver. Although both rat strains retained 4-OH-2,3,5,3',4'-pentaCB in serum, Gunn rats also retained the catechol PCBs, accounting for about 52% of the total phenolic PCBs. These results suggest that a lack of UGTs markedly alters the formation ratios and retention profiles of catechols and MeSO2 metabolites of PCBs.
Haraguchi
Koichi
K
Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan. ko-ichi@ka2.so-net.ne.jp
Kato
Yoshihisa
Y
Koga
Nobuyuki
N
Degawa
Masakuni
M
D000818:Animals; D002396:Catechols / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D014453:Glucuronosyltransferase / Q000172:deficiency / Q000235:genetics; D008099:Liver / Q000737:chemistry; D008297:Male; D011078:Polychlorinated Biphenyls / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011911:Rats, Gunn; D018629:Spectrometry, Mass, Secondary Ion; D000099148:UGT1A1 Enzyme
D002396:Catechols; D014453:Glucuronosyltransferase; D011078:Polychlorinated Biphenyls; D000099148:UGT1A1 Enzyme; C477388:KC 500; C499946:Ugt1a1 protein, rat; C009828:2,4,5,2',5'-pentachlorobiphenyl