Djuric Z, McGunagle D L
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 48201.
Cancer Lett. 1989 Nov 15;48(1):13-8. doi: 10.1016/0304-3835(89)90197-3.
1,6-Dinitropyrene is a carcinogenic environmental pollutant that is activated to a DNA binding species via nitroreduction. The major reduced metabolite of 1,6-dinitropyrene in aerobic incubations with rat liver cytosol is 1-nitro-6-nitrosopyrene, and further reduction of this metabolite results in formation of DNA-reactive species. We were able to separate the nitroreductase activity in rat liver cytosol from the nitrosoreductase activity by gel filtration. The ability of the nitroreductase to reduce 1,6-dinitropyrene was not affected by the presence of oxygen. Reduction of 1-nitro-6-nitrosopyrene is catalyzed by different enzymes and results in formation of metabolites which can react with oxygen. In aerobic incubations with cytosol, this reaction of reduced intermediates with oxygen does not decrease the binding of 1,6-dinitropyrene to DNA. The ability of rat liver enzymes to reduce 1,6-dinitropyrene to reactive intermediates in the presence of oxygen may be an important factor contributing to the potent tumorigenicity of this compound.
1,6-二硝基芘是一种致癌性环境污染物，可通过硝基还原作用被激活为与DNA结合的物质。在与大鼠肝细胞溶胶进行需氧孵育时，1,6-二硝基芘的主要还原代谢产物是1-硝基-6-亚硝基芘，该代谢产物的进一步还原会导致形成与DNA发生反应的物质。我们通过凝胶过滤能够将大鼠肝细胞溶胶中的硝基还原酶活性与亚硝基还原酶活性分离。硝基还原酶还原1,6-二硝基芘的能力不受氧气存在的影响。1-硝基-6-亚硝基芘的还原由不同的酶催化，并导致形成可与氧气发生反应的代谢产物。在与细胞溶胶进行需氧孵育时，还原中间体与氧气的这种反应不会降低1,6-二硝基芘与DNA的结合。在氧气存在的情况下，大鼠肝脏酶将1,6-二硝基芘还原为反应性中间体的能力可能是导致该化合物具有强大致癌性的一个重要因素。
