Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer.
Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer.
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DOI：
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发表时间：
1984-11
期刊：
影响因子：
11.2
通讯作者：
J. Mohandas;J. J. Marshall-J.;G. Duggin;J. Horvath;D. Tiller
中科院分区：
文献类型：
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作者：
J. Mohandas;J. J. Marshall-J.;G. Duggin;J. Horvath;D. Tiller
本实验通过对家兔膀胱移行上皮（UBTE）、膀胱非移行组织（UBNT）和肝脏中还原型谷胱甘肽（GSH）含量及GSH相关酶活性的比较研究，探讨了UBTE对过氧化物酶介导的化学致癌作用敏感的原因。前列腺素H合酶对化学致癌物的共氧化活化在UBTE中以高水平发生，在UBNT中以最低水平发生。其他过氧化物酶也可能激活膀胱中的致癌异生物质。UBTE和UBNT中的GSH浓度低于肝脏中的GSH浓度。γ-谷氨酰转肽酶活性在UBTE和UBNT中比在肝脏中低得多。在UBTE和UBNT中，硒依赖性和硒非依赖性谷胱甘肽过氧化物酶的活性都很低。在UBTE中，细胞溶质谷胱甘肽S-转移酶对1，2-环氧-（4-硝基苯氧基）丙烷的活性非常低。微粒体谷胱甘肽S-转移酶对1-氯-2，4-二硝基苯的活性在UBTE中比在肝脏中低得多。我们建议，低GSH浓度和谷胱甘肽过氧化物酶，γ-谷氨酰转肽酶，谷胱甘肽S-转移酶的某些同工酶的活动减少可能是负责的UBTE对化学致癌的脆弱性。
A comparative study of reduced glutathione (GSH) concentrations and activities of GSH related-enzymes in urinary bladder transitional epithelium (UBTE), urinary bladder nontransitional tissue (UBNT), and liver of the rabbit, was carried out to investigate the reasons for the susceptibility of UBTE towards peroxidase-mediated chemical carcinogenesis. Cooxidative activation of chemical carcinogens by prostaglandin H synthase occurs at high levels in UBTE and minimally in UBNT. Other peroxidases are also likely to activate carcinogenic xenobiotics in the urinary bladder. GSH concentrations in UBTE and UBNT were low compared to that in the liver. gamma-Glutamyl transpeptidase activities were much lower in UBTE and in UBNT than those in the liver. Activities of selenium-dependent and selenium-independent glutathione peroxidases were very low in UBTE and UBNT. Cytosolic glutathione S-transferase activity towards 1,2-epoxy-(4-nitrophenoxy)propane was very low in UBTE. Microsomal glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene was much lower in UBTE than in the liver. We propose that the low GSH concentration and diminished activities of glutathione peroxidases, gamma-glutamyl transpeptidase, and certain isozymes of glutathione S-transferase could be responsible for the vulnerability of UBTE towards chemical carcinogenesis.