Hesse S, Mezger M, Wolff T
Chem Biol Interact. 1978 Mar;20(3):355-65. doi: 10.1016/0009-2797(78)90113-8.
The irreversible binding of [14C] 2,2'-di- and [14C] 2,4,5,2',4',5'-hexachlorobiphenyl ([14C] DCB and [14C] HCB) to protein was studied in the presence of rat liver microsomes and a NADPH-generating system. Protein-bound radioactivity was found with [14C] DCB but not with [14C] HCB. The binding of 14C-metabolites was increased by pretreatment of the rats with phenobarbital or polychlorinated biphenyls. Protein binding was linear for 80 min. In contrast, monohydroxy-metabolites of DCB were formed and degraded within 40 min. Inhibition of secondary oxidation of DCB by scavenging superoxide anions or by glucuronidation of the monophenols markedly decreased the protein binding. Addition of trichloropropene oxide or styrene oxide, both inhibitors of epoxide hydrase, did not significantly stimulate the binding. The results suggest that the majority of reactive metabolites of DCB arise from secondary metabolism, i.e., the subsequent oxidation of the phenolic metabolites. Arene oxides, the primary products, appear to play a minor role in the protein binding of DCB.
在大鼠肝微粒体和NADPH生成系统存在的情况下，研究了[14C] 2,2'-二氯联苯和[14C] 2,4,5,2',4',5'-六氯联苯（[14C] DCB和[14C] HCB）与蛋白质的不可逆结合。发现[14C] DCB能与蛋白质结合放射性，但[14C] HCB不能。用苯巴比妥或多氯联苯预处理大鼠后，14C代谢物的结合增加。蛋白质结合在80分钟内呈线性。相比之下，DCB的单羟基代谢物在40分钟内形成并降解。通过清除超氧阴离子或通过单酚的葡萄糖醛酸化抑制DCB的二次氧化，显著降低了蛋白质结合。添加环氧氯丙烷或环氧苯乙烷这两种环氧水解酶抑制剂，并未显著刺激结合。结果表明，DCB的大多数活性代谢物来自二次代谢，即酚类代谢物的后续氧化。作为主要产物的芳烃氧化物，在DCB与蛋白质的结合中似乎起次要作用。
