Sinclair P R, Sinclair J F, Bement W J, Lambrecht R W, Bonkovsky H L
IARC Sci Publ. 1986(77):535-42.
Chick-embryo liver cells in culture were used to study the mechanism by which hexachlorobenzene (HCB) and other chlorobenzenes cause hepatic porphyria with accumulation of uroporphyrin (URO). The actions of the chlorobenzenes were similar to those of 3,4,3',4'-tetrachlorobiphenyl (TCB), but pretreatment with 3-methylcholanthrene (MC) or hexachlorobenzene was needed for maximum accumulation of URO. HCB was as potent and almost as rapid as the biphenyl in causing URO accumulation, but tetrachlorobenzenes caused little URO accumulation. Ellipticine, an inhibitor of cytochrome P-448, stopped the accumulation of URO. A mechanism is proposed for the action of the chlorobenzenes that involves binding to cytochrome P-448 and production of active oxygen species that oxidize uroporphyrinogen.
培养的鸡胚肝细胞被用于研究六氯苯（HCB）和其他氯苯导致肝性卟啉症并伴有尿卟啉（URO）蓄积的机制。氯苯的作用与3,4,3',4'-四氯联苯（TCB）相似，但为使URO最大程度蓄积，需要用3-甲基胆蒽（MC）或六氯苯进行预处理。HCB在引起URO蓄积方面与联苯一样有效且几乎同样迅速，但四氯苯几乎不引起URO蓄积。细胞色素P-448的抑制剂椭圆玫瑰树碱可阻止URO的蓄积。提出了一种氯苯作用机制，该机制涉及与细胞色素P-448结合并产生活性氧物种，活性氧物种可氧化尿卟啉原。
