Wise R W, Zenser T V, Rice J R, Davis B B
Carcinogenesis. 1986 Jan;7(1):111-5. doi: 10.1093/carcin/7.1.111.
Metabolism of benzidine was assessed with rabbit renal inner medullary slices. 3-(Glutathion-S-yl)-benzidine was identified as a product of metabolism. This thioether conjugate was shown to be identical to synthetic conjugate by chromatographically assisted hydrodynamic voltammetric and enzymatic techniques. A good correlation between PGE2 synthesis and conjugate formation was observed with a variety of incubation conditions including tissue weight, arachidonic acid concentration and incubation time. With 0-0.01 mM idomethacin, an inhibitor of the fatty acid cyclo-oxygenase component of prostaglandin H synthase (PHS), a linear relationship between conjugate formation and prostaglandin E2 synthesis was observed. In contrast, the peroxidase cosubstrates propylthiouracil, phenidone, ascorbate and methimazole inhibited arachidonic acid stimulation of conjugate formation but not prostaglandin E2 synthesis. These cosubstrates may be functioning as competitive inhibitors of benzidine co-oxidation. The results are consistent with peroxidatic metabolism of benzidine in intact tissue by a PHS-mediated process. 3-(Glutathion-S-yl)-benzidine may be a useful marker for studying peroxidatic metabolism in intact tissue and in investigating selective inhibition of this process.
用兔肾内髓切片评估联苯胺的代谢。3-(谷胱甘肽-S-基)-联苯胺被鉴定为代谢产物。通过色谱辅助的流体动力伏安法和酶学技术表明，这种硫醚共轭物与合成共轭物相同。在包括组织重量、花生四烯酸浓度和孵育时间在内的各种孵育条件下，观察到前列腺素E2合成与共轭物形成之间有良好的相关性。使用0-0.01 mM消炎痛（一种前列腺素H合酶（PHS）脂肪酸环氧化酶成分的抑制剂）时，观察到共轭物形成与前列腺素E2合成之间呈线性关系。相比之下，过氧化物酶共底物丙硫氧嘧啶、非那西丁、抗坏血酸和甲巯咪唑抑制花生四烯酸对共轭物形成的刺激，但不抑制前列腺素E2合成。这些共底物可能作为联苯胺共氧化的竞争性抑制剂发挥作用。结果与完整组织中联苯胺通过PHS介导的过程进行过氧化物代谢一致。3-(谷胱甘肽-S-基)-联苯胺可能是研究完整组织中过氧化物代谢以及研究该过程选择性抑制的有用标志物。
