Ohta Chiho, Haraguchi Koichi, Kato Yoshihisa, Endo Tetsuya, Koga Nobuyuki
Faculty of Nutritional Sciences, Nakamura Gakuen University, 5-7-1 Befu, Johnan-ku, Fukuoka 814-0198.
Fukuoka Igaku Zasshi. 2011 Apr;102(4):167-74.
Our preceding studies reported using animal liver microsomes that 2, 2', 3, 4, 4', 5'-hexachlorobiphenyl (hexaCB) (CB138), a worldwide and persistent organohalogen pollutant, was metabolized to two major hydroxy (OH)-metabolites, 3'-OH-CB138 (M-3) and 2'-OH-2, 3, 3', 4, 4', 5'-hexaCB (M-4), and two dechlorinated OH-metabolites (M-1 and M-2) in guinea pigs at much faster rate than in rats and hamsters. In this study, the distribution of four CB138 metabolites to the serum and liver 4 days after exposure and their fecal excretion were studied in guinea pigs administered with CB138 intraperitoneally. 3'-OH-CB138 (M-3) was a major metabolite in the liver, serum and feces. M-1 was observed as a minor metabolite in guinea pig feces. In contrast, trace amount of M-2 was present in guinea pig serum. However, 2'-OH-2, 3, 4, 3', 4', 5'-hexaCB (M-4) which was a major metabolite in the in vitro system using guinea pig liver microsomes was not found in all tissues and feces tested in this study. On the other hand, the exact chemical structures of M-1 and M-2 were determined to be 6'-OH-2, 3, 3', 4, 4'-pentaCB and 4'-OH-2, 2', 3, 4, 5'-pentaCB, respectively, by comparison of the retention time and mass fragmentation of the synthetic authentic samples in GC-MS. From these results, it is suggested that the metabolism of CB138 in guinea pigs may proceed by three pathways, a direct hydroxylation at 3'-position, and also the formation of 2',3'- or 3', 4'-epoxide and subsequent dechlorination and that three metabolites show the different mode of distribution and excretion.
我们之前的研究报道，使用动物肝脏微粒体时发现，2,2',3,4,4',5'-六氯联苯（六氯联苯，CB138）作为一种全球范围内广泛存在的持久性有机卤素污染物，在豚鼠体内代谢为两种主要的羟基（OH）代谢物，即3'-OH-CB138（M-3）和2'-OH-2,3,3',4,4',5'-六氯联苯（M-4），以及两种脱氯的OH代谢物（M-1和M-2），其代谢速度比大鼠和仓鼠快得多。在本研究中，对腹腔注射CB138的豚鼠在暴露4天后，四种CB138代谢物在血清和肝脏中的分布及其粪便排泄情况进行了研究。3'-OH-CB138（M-3）是肝脏、血清和粪便中的主要代谢物。M-1在豚鼠粪便中作为次要代谢物被观察到。相比之下，豚鼠血清中仅存在痕量的M-2。然而，在本研究测试的所有组织和粪便中均未发现2'-OH-2,3,4,3',4',5'-六氯联苯（M-4），而在使用豚鼠肝脏微粒体的体外系统中，M-4是主要代谢物。另一方面，通过气相色谱-质谱联用（GC-MS）比较合成标准样品的保留时间和质量碎片，确定M-1和M-2的确切化学结构分别为6'-OH-2,3,3',4,4'-五氯联苯和4'-OH-2,2',3,4,5'-五氯联苯。从这些结果表明，豚鼠体内CB138的代谢可能通过三条途径进行，即3'-位的直接羟基化，以及2',3'-或3',4'-环氧化物的形成及随后的脱氯反应，并且三种代谢物表现出不同的分布和排泄模式。
