Cantoni L, Rizzardini M, Tacconi M T, Graziani A
Toxicology. 1987 Sep;45(3):291-305. doi: 10.1016/0300-483x(87)90019-9.
The effect of hexachlorobenzene (HCB) on microsomal cytochromes P-450 and b5, monooxygenase activity and membrane composition was examined in male and female Fischer rats. Cytochrome P-450 was induced more in male than in female animals while cytochrome b5 was induced only in males. Analysis of patterns of induction of microsomal monooxygenases showed that aminopyrine-N-demethylase activity doubled in both sexes after treatment while aryl hydrocarbon hydroxylase activity was 16 times the control value in the females and 1.5 times in the males. After HCB treatment the phospholipid content of microsomal membranes per gram of liver was increased in both sexes while cholesterol was unchanged. Analysis of the phospholipids (PL) pattern showed that the percentage of sphingomyelin (SPH) decreased significantly (50% of the control value) while phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) did not change. These changes resulted in a reduction of membrane microviscosity and indicate that HCB interferes with the biosynthesis of phospholipids containing choline. Free fatty acid (FFA) content also dropped in both sexes but females were more affected; free arachidonic acid rose in females. HCB induction of microsomal cytochromes and monooxygenases is thus accompanied by marked modifications of membrane composition. Comparing the 2 sexes, HCB showed more pronounced features of 'PB type' inducers in males.
研究了六氯苯（HCB）对雄性和雌性Fischer大鼠微粒体细胞色素P - 450和b5、单加氧酶活性及膜组成的影响。细胞色素P - 450在雄性动物中的诱导程度高于雌性，而细胞色素b5仅在雄性中被诱导。对微粒体单加氧酶诱导模式的分析表明，处理后两性的氨基比林 - N - 脱甲基酶活性均增加了一倍，而芳烃羟化酶活性在雌性中是对照值的16倍，在雄性中是对照值的1.5倍。HCB处理后，两性每克肝脏微粒体膜的磷脂含量均增加，而胆固醇含量不变。对磷脂（PL）模式的分析表明，鞘磷脂（SPH）的百分比显著降低（为对照值的50%），而磷脂酰胆碱（PC）、磷脂酰肌醇（PI）和磷脂酰乙醇胺（PE）没有变化。这些变化导致膜微粘度降低，表明HCB干扰了含胆碱磷脂的生物合成。两性的游离脂肪酸（FFA）含量也均下降，但雌性受影响更大；雌性中游离花生四烯酸升高。因此，HCB对微粒体细胞色素和单加氧酶的诱导伴随着膜组成的显著改变。比较两性，HCB在雄性中表现出更明显的“PB型”诱导剂特征。
