Dutcher J S, Sun J D, Bechtold W E, Unkefer C J
Fundam Appl Toxicol. 1985 Apr;5(2):287-96. doi: 10.1016/0272-0590(85)90076-4.
Many nitro-substituted polycyclic aromatic hydrocarbons (NPAHs) have been identified as environmental pollutants and have been found to be mutagens and carcinogens in bacteria and mammalian systems. They require metabolism to express their biological activity. The metabolism and excretion of 1-nitropyrene (NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal (ip) or oral administration was studied. Radiolabeled NP was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of [14C]NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered 14C was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3-8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37 degrees C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible.
许多硝基取代的多环芳烃（NPAHs）已被确认为环境污染物，并且在细菌和哺乳动物系统中被发现是诱变剂和致癌剂。它们需要通过代谢来表达其生物活性。研究了Fischer-344大鼠腹腔内（ip）或口服给予常见的NPAH 1-硝基芘（NP）后的代谢和排泄情况。将放射性标记的NP给予大鼠（10 mg NP/kg体重），并收集尿液和粪便7天。腹腔注射[14C]NP后，60%的放射性出现在尿液中，20%出现在粪便中。同样，口服14C后，分别有55%和35%出现在尿液和粪便中。尿液和粪便均通过高压液相色谱法分析代谢产物。尿液和粪便中的大部分放射性与极性很强的代谢产物相关，没有一种代谢产物占剂量的比例超过10%。检测到少量（剂量的不到1%）的氨基芘（AP）、乙酰氨基芘和NP。发现一种尿液代谢产物（剂量的3-8%），当尿液在37℃、pH 4.5条件下过夜加热时会转化为乙酰氨基芘酚（两种异构体）。口服NP后比腹腔注射后排出更多的这种代谢产物（2.2倍）以及AP（1.8倍）。本研究中发现的NP代谢产物表明，硝基的还原是大鼠体内NP代谢的重要途径。由于硝基还原似乎是NPAHs激活细菌诱变剂所必需的，这表明大鼠体内存在类似的代谢途径（由哺乳动物和/或肠道细菌酶催化），并且通过硝基还原将NPAHs激活为致癌物或毒素是可能的。
