Djurić Z, Potter D W, Heflich R H, Beland F A
Chem Biol Interact. 1986 Oct 1;59(3):309-24. doi: 10.1016/s0009-2797(86)80076-x.
Nitrated pyrenes are mutagenic and tumorigenic environmental pollutants that are activated to DNA-binding derivatives via nitroreduction. We have investigated the enzymatic nitroreduction of 1-nitropyrene, 1,3-, 1,6- and 1,8-dinitropyrene to determine if differences in the extent of nitroreduction may help explain differences in their biological potencies. Each nitrated pyrene was incubated aerobically and anaerobically with 105,000 X g supernatant (S105) from Salmonella typhimurium TA98 and the nitroreductase-deficient strain, TA98NR, and with cytosol and microsomes from rat and human liver. Under anaerobic conditions, 1-nitropyrene and 1,3-dinitropyrene were reduced by TA98 S105 to a lesser extent than 1,6- and 1,8-dinitropyrene. The extent of 1,6- and 1,8-dinitropyrene metabolism was not altered relative to TA98 when using TA98NR S105, but the nitroreduction of 1-nitropyrene and 1,3-dinitropyrene was decreased. Both rat and human liver cytosol and microsomes reduced 1,6- and 1,8-dinitropyrene to greater extents than 1-nitropyrene and 1,3-dinitropyrene. Under aerobic conditions rat and human liver cytosols were similar to TA98 S105 in that aminopyrene decreased while nitrosopyrene formation increased. By comparison, oxygen decreased the microsomal formation of both nitrosopyrenes and aminopyrenes. The reduction of succinoylated cytochrome c was measured during the hepatic metabolism of nitro- and nitrosopyrenes under aerobic conditions. The data indicated that reduced nitro- and nitrosopyrene intermediates were directly reducing succinoylated cytochrome c and that the assay could be used as a measure of aerobic nitroreduction. These studies demonstrate that 1,6- and 1,8-dinitropyrene are reduced to a greater extent than 1-nitropyrene and 1,3-dinitropyrene, which corresponds to their relative biological potencies as mutagens and carcinogens. Furthermore, although more extensive nitroreduction is detected under anaerobic conditions, the nitroreduction that occurs aerobically may be important for the mutagenic and tumorigenic properties of these compounds.
硝化芘是具有致突变性和致癌性的环境污染物，可通过硝基还原作用被激活为与DNA结合的衍生物。我们研究了1-硝基芘、1,3-、1,6-和1,8-二硝基芘的酶促硝基还原作用，以确定硝基还原程度的差异是否有助于解释它们生物活性的差异。将每种硝化芘分别与鼠伤寒沙门氏菌TA98及其硝基还原酶缺陷菌株TA98NR的105,000×g上清液（S105），以及大鼠和人肝脏的胞质溶胶和微粒体在需氧和厌氧条件下进行孵育。在厌氧条件下，TA98 S105对1-硝基芘和1,3-二硝基芘的还原程度低于1,6-和1,8-二硝基芘。当使用TA98NR S105时，1,6-和1,8-二硝基芘的代谢程度相对于TA98没有改变，但1-硝基芘和1,3-二硝基芘的硝基还原作用减弱。大鼠和人肝脏的胞质溶胶和微粒体对1,6-和1,8-二硝基芘的还原程度均高于1-硝基芘和1,3-二硝基芘。在需氧条件下，大鼠和人肝脏的胞质溶胶与TA98 S105相似，即氨基芘减少而亚硝基芘的形成增加。相比之下，氧气会减少微粒体中亚硝基芘和氨基芘的形成。在需氧条件下，在硝基芘和亚硝基芘的肝脏代谢过程中测量琥珀酰化细胞色素c的还原情况。数据表明，还原的硝基芘和亚硝基芘中间体直接还原琥珀酰化细胞色素c，该测定可用于衡量需氧硝基还原作用。这些研究表明，1,6-和1,8-二硝基芘的还原程度高于1-硝基芘和1,3-二硝基芘，这与它们作为诱变剂和致癌物的相对生物活性相对应。此外，尽管在厌氧条件下检测到更广泛的硝基还原作用，但需氧条件下发生的硝基还原作用可能对这些化合物的致突变性和致癌性很重要。
