Oguri K, Koga Y, Tsuda M, Ariyoshi N, Ishii Y, Yamada H, Yoshimura H
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka.
Fukuoka Igaku Zasshi. 1993 May;84(5):175-80.
The induction of liver microsomal UDP-glucuronyltransferase (UGT) activity toward bilirubin by pretreatment with 3, 4, 3', 4'-tetrachlorobiphenyl (TCB), 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) and 3-methylcholanthrene (MC) was studied in guinea pigs and rats. In addition, microsomal benzo(a)pyrene 3-hydroxylase and cytosolic DT-diaphorase activities were also measured for the comparison. All of the PenCB, TCB and MC significantly induced the bilirubin UGT activity of guinea pig liver microsomes. The highest induction (6-fold over the control) was seen in the PenCB-treated animal, and MC (3.2-fold) and TCB (2.4-fold) were less effective. On the other hand, the induction of benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities of guinea pigs was not so remarkable as that of bilirubin UGT activity. In the guinea pig, the inducibility of bilirubin UGT activity seemed to be correlated with the toxicity induced with PenCB, TCB and MC. In contrast to the guinea pig, UGT activity toward bilirubin in the rat was significantly decreased by the treatment with the inducers described above. These results suggest that bilirubin UGT activity in the guinea pig can be an index for the toxicity of polychlorinated biphenyls as like as benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities in the rat.
在豚鼠和大鼠中研究了用3,4,3',4'-四氯联苯(TCB)、3,4,5,3',4'-五氯联苯(PenCB)和3-甲基胆蒽(MC)预处理对肝脏微粒体胆红素UDP-葡萄糖醛酸基转移酶(UGT)活性的诱导作用。此外,还测定了微粒体苯并(a)芘3-羟化酶和胞质DT-黄递酶活性以作比较。所有的PenCB、TCB和MC均显著诱导豚鼠肝脏微粒体的胆红素UGT活性。PenCB处理的动物诱导作用最强(比对照高6倍),MC(3.2倍)和TCB(2.4倍)的诱导作用较弱。另一方面,豚鼠苯并(a)芘3-羟化酶和DT-黄递酶活性的诱导不如胆红素UGT活性显著。在豚鼠中,胆红素UGT活性的诱导性似乎与PenCB、TCB和MC诱导的毒性相关。与豚鼠相反,用上述诱导剂处理大鼠后,其对胆红素的UGT活性显著降低。这些结果表明,豚鼠中的胆红素UGT活性可作为多氯联苯毒性的一个指标,就如同大鼠中的苯并(a)芘3-羟化酶和DT-黄递酶活性一样。