[Species differences in the in vitro metabolism of 2,4,5,2',3',4'-hexachlorobiphenyl].
In vitro Metabolism of 2,4,5,2',3',4'-hexachlorobiphenyl (CB138) was studied using liver microsomes from rats, hamsters and guinea pigs. Guinea pig liver microsomes formed four metabolites named as M-1, M-2, M-3 and M-4 and these metabolites were all increased to about 4-5 fold of untreated microsomes by pretreatment of phenobarbital. Liver microsomes of rats and hamsters showed much less activity to metabolize CB138 than those of guinea pigs. Only phenobarbital-treated microsomes produced very small amounts of M-3 in rats and M-1, M-2 and M-3 in hamsters, but untreated and MC-treated microsomes did not. When mass spectra of the methylated derivatives of M-1, M-2, M-3 and M-4 were measured in GC/MS, the former two possess the molecular ion of 354 and the latter two had the molecular ion of 388. In addition, the mass fragmentation pattern indicated that M-1, M-2, M-3 and M-4 are 2-OH-4,5,2',3',4'-pentachlorobiphenyl, 5-OH-2,4,2',3',4'-pentachlorobiphenyl, 3-OH-CB138 and 2-OH-3,4,5,2',3',4'-hexachlorobiphenyl, respectively. Of four metabolites, the chemical structures of M-3 and M-4 were supported by the synthesized authentic compounds. From these results, it is suggested that the metabolism of CB138 in guinea pig liver proceeds mainly via 2,3-epoxide as an intermediate and a PB-inducible P450, CYP2B18, is the most important isozyme in CB138 metabolism.
Koga
N
N
Department of Food and Nutrition, Nakamura Gakuen University, 5-7-1, Befu, Johnan-ku, Fukuoka 814-0198.
Kanamaru
T
T
Oishi
N
N
Kato
Y
Y
Kimura
R
R
Haraguchi
K
K
Masuda
Y
Y
D000818:Animals; D006224:Cricetinae; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D008099:Liver / Q000378:metabolism*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013057:Spectrum Analysis
C433840:2,4,5,2',3',4'-hexachlorobiphenyl; D011078:Polychlorinated Biphenyls