Hanioka N, Saeki H K, Ishida C, Koga N, Yoshimura H
Department of Hygienic and Forensic Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka.
Fukuoka Igaku Zasshi. 1991 May;82(5):191-6.
We observed previously that polychlorinated biphenyl (PCB) could be classified to two groups, 3-methylcholanthrene (MC)-type and phenobarbital (PB)-type, in term of inducibility of the hepatic enzymes. MC-type PCBs such as 3,4,3',4'-tetrachlorobiphenyl (TCB), 3,4,5,3',4'-pentachlorobiphenyl (PenCB) and 3,4,5,3',4',5'-hexachlorobiphenyl (HexCB) exhibited high acute toxicity in parallel with their induction ability of microsomal benzo[a]pyrene 3-hydroxylase and cytosolic DT-diaphorase. On the contrary, PB-type PCBs such as 2,5,2',5'-TCB and 2,4,5,2',4',5'-HexCB which induce microsomal benzphetamine N-demethylase and NADPH-cytochrome P-450 reductase activities showed virtually no or very low toxicity. In the present study, we examined effects of 2,5,2',5'-TCB and its major metabolite 3-hydroxy-2,5,2',5'-TCB on body weight gain, organ weights and activities of hepatic enzymes in rats and assessed acute toxicity of these compounds. As the results, in both 2,5,2',5'-TCB and 3-hydroxy-2,5,2',5'-TCB groups, the body weights were increased during the experiment, but the rate of growth was significantly suppressed after 3 days. Significant hypertrophy of the liver and decrease of total liver lipid content were observed in 2,5,2',5'-TCB group, but the atrophy of spleen and thymus was not affected in both groups. On the other hand, in 2,5,2',5'-TCB group, benzo[a]pyrene 3-hydroxylase and benzphetamine N-demethylase activities were increased to 2. 4-fold and 1.5-fold, respectively, but were not increased in 3-hydroxy-2,5,2',5'-TCB group. After injection of 2,5,2',5'-TCB, 45% of the dose was excreted as 3-hydroxy-2,5,2',5'-TCB in feces for 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前观察到,就肝酶的诱导性而言,多氯联苯(PCB)可分为两组,即3-甲基胆蒽(MC)型和苯巴比妥(PB)型。MC型多氯联苯,如3,4,3',4'-四氯联苯(TCB)、3,4,5,3',4'-五氯联苯(PenCB)和3,4,5,3',4',5'-六氯联苯(HexCB),表现出高急性毒性,同时具有微粒体苯并[a]芘3-羟化酶和胞质DT-黄递酶的诱导能力。相反,诱导微粒体苄非他明N-脱甲基酶和NADPH-细胞色素P-450还原酶活性的PB型多氯联苯,如2,5,2',5'-TCB和2,4,5,2',4',5'-HexCB,实际上没有毒性或毒性非常低。在本研究中,我们检测了2,5,2',5'-TCB及其主要代谢产物3-羟基-2,5,2',5'-TCB对大鼠体重增加、器官重量和肝酶活性的影响,并评估了这些化合物的急性毒性。结果显示,在2,5,2',5'-TCB组和3-羟基-2,5,2',5'-TCB组中,实验期间体重均增加,但3天后生长速率显著受到抑制。在2,5,2',5'-TCB组中观察到肝脏显著肥大和肝脏总脂质含量降低,但两组中脾脏和胸腺的萎缩均未受到影响。另一方面,在2,5,2',5'-TCB组中,苯并[a]芘3-羟化酶和苄非他明N-脱甲基酶活性分别增加至2.4倍和1.5倍,但在3-羟基-2,5,2',5'-TCB组中未增加。注射2,5,2',5'-TCB后,5天内45%的剂量以3-羟基-2,5,2',5'-TCB的形式随粪便排出。(摘要截选至250词)