Seki Y, Kawanishi S, Sano S
Department of Public Health, Faculty of Medicine, Kyoto University, Japan.
Ann N Y Acad Sci. 1987;514:222-34. doi: 10.1111/j.1749-6632.1987.tb48777.x.
PCBs are known to be potent inducers of chemical porphyria. We studied the structure-activity relationship of synthetic PCBs as porphyrin inducers and found that 3,4,3',4'-tetrachlorobiphenyl, 3,4,3',4',5'-pentachlorobiphenyl, and 3,4,5,3',4',5'-hexachlorobiphenyl were the most active inducers. The structural requirement for potent porphyrinogenic activity of PCB isomers was the substitution of chlorine atoms at the para and meta positions. Isomers fulfilling this requirement had more highly conjugated and nearly coplanar conformations. In addition, it was demonstrated that inhibition of UROD by the most active porphyrin inducers occurred in vitro using purified enzyme. These findings could explain how porphyrinogenic PCBs, by primarily inhibiting UROD and hence depleting heme, ultimately increase ALAS synthesis. The outbreak of yusho disease in Japan (which was caused by PCB-contaminated rice oil) and a similar episode of food poisoning in Taiwan (which was also related to PCB contamination) were discussed, particularly with reference to urinary porphyrin levels and clinical response.
多氯联苯是已知的化学性卟啉症的强效诱导剂。我们研究了合成多氯联苯作为卟啉诱导剂的构效关系，发现3,4,3',4'-四氯联苯、3,4,3',4',5'-五氯联苯和3,4,5,3',4',5'-六氯联苯是最活跃的诱导剂。多氯联苯异构体产生强效卟啉原活性的结构要求是在对位和间位有氯原子取代。满足这一要求的异构体具有更高的共轭性和近乎共面的构象。此外，使用纯化酶在体外证明了最活跃的卟啉诱导剂对尿卟啉原脱羧酶（UROD）有抑制作用。这些发现可以解释产生卟啉的多氯联苯如何主要通过抑制尿卟啉原脱羧酶从而消耗血红素，最终增加δ-氨基-γ-酮戊酸合成酶（ALAS）的合成。文中讨论了日本的油症疫情（由多氯联苯污染的米糠油引起）和台湾的类似食物中毒事件（也与多氯联苯污染有关），特别是参考了尿卟啉水平和临床反应。
