代谢
这些调查的目的是确定大鼠肺中/nitroPAHs/（包括3,9-DNF...）的代谢活化途径。比较了原始大鼠和预先用3-甲基胆蒽（3-MC）或苯巴比妥处理的、能诱导细胞色素P450酶的大鼠肺亚细胞组分的NFs代谢率。在缺氧条件下孵育大鼠肺细胞质后，检测到一个主要代谢物，即氨基酸衍生物...。3,9-DNF被代谢为其氨基酸衍生物，即氨基硝基荧蒽...。用3-MC或苯巴比妥预处理大鼠并不影响细胞质还原的代谢率。3-NF和3,9-DNF都在缺氧条件下通过微粒体还原酶代谢为它们的氨基酸衍生物。3,9-DNF的代谢速度是3-NF的两倍。从3-MC诱导的大鼠的微粒体中，氨基硝基荧蒽代谢物的形成增加了大约2倍，而苯巴比妥处理的大鼠的微粒体对此无影响。这表明，3-MC诱导的细胞色素P450同种型和还原酶可能参与了3-NF和3,9-DNF的代谢。...在富氧条件下，没有检测到大鼠肺微粒体对3,9-DNF的代谢。因此，在3,9-DNF的代谢中抑制了环羟基化，主要途径是硝基还原。3,9-DNF在缺氧条件下的代谢速率高于3-NF，以及预期由3,9-DNF形成的假定N-乙酰氧基衍生物的高反应性，可能是这两种致癌物诱导肺癌差异毒力的原因。
The purpose of these investigations was to determine the activation pathways in the rat lung for the metabolism of the /nitroPAHs/ including ... 3,9-DNF... . The metabolic rates of NFs were compared for lung subcellular fractions of pristine rats as well as rats previously treated with 3-methylcholanthrene (3-MC) or phenobarbital at levels that would induce cytochrome P450 enzymes. One major metabolite, the amino derivative, was detected ... following anaerobic incubation of rat lung cytosol... . 3,9-DNF was metabolized to its amino derivative, aminonitrofluoranthene... . Pretreatment of the rats with 3-MC or phenobarbital did not affect the metabolic rates of cytosolic reduction. Both 3-NF and 3,9-DNF were metabolized anaerobically to their amino derivatives by microsomal reductase(s). 3,9-DNF was metabolized twice as fast as 3-NF. The formation of the aminonitrofluoranthene metabolite was increased approximately 2 times with microsomes from 3-MC-induced rats, but was unaffected by microsomes from phenobarbital-treated rats. This suggests that the cytochrome P450 isozymes and reductase, which are induced by 3-MC, may be involved in the metabolism of 3-NF and 3,9-DNF. ... 3,9-DNF metabolism was not detected aerobically with lung microsomes. Thus, ring hydroxylation was inhibited in the metabolism of 3,9-DNF, and the major pathway was nitroreduction. This higher rate of anaerobic metabolism of 3,9-DNF over 3-NF and the expected high reactivity of the putative N-acetoxy derivative formed from 3,9-DNF may be responsible for the differential potency for lung cancer induction by these two carcinogens.
来源:Hazardous Substances Data Bank (HSDB)
