George S E, Chadwick R W, Kohan M J, Allison J C, Williams R W, Chang J
Genetic Toxicology Division (MD 68A), U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Cancer Lett. 1994 May 16;79(2):181-7. doi: 10.1016/0304-3835(94)90258-5.
After male germ-free and conventionalized Fischer 344 rats were administered per os (p.o.) 75 mg/kg 2,6-DNT, intestinal nitroreductase, beta-glucuronidase, and azo reductase activities were lower in the cecum and large intestine of germ-free animals. However, there was no significant difference in the small intestinal nitroreductase and azo reductase compared to the conventionalized counterparts. This indicated a potential mucosal source for the enzymes. Urines from germ-free rats (1144 +/- 64 revertants/ml) were less mutagenic than those from conventionalized animals (1467 +/- 171 revertants/ml) in Salmonella typhimurium strain TA98 without S9. In the presence of S9, urine from conventionalized animals (894 +/- 56 revertants/ml) was more mutagenic than that from germ-free rats (686 +/- 60 revertants/ml). The presence of the intestinal flora plays an important role in the activation of 2,6-DNT but other metabolic pathways, such as the small intestinal mucosal and/or hepatic enzymes, are present that can generate excreted genotoxicants.
给雄性无菌和定殖化的Fischer 344大鼠经口给予75 mg/kg的2,6 -二硝基甲苯（2,6 - DNT）后，无菌动物盲肠和大肠中的肠道硝基还原酶、β - 葡萄糖醛酸酶和偶氮还原酶活性较低。然而，与定殖化大鼠相比，小肠中的硝基还原酶和偶氮还原酶没有显著差异。这表明这些酶可能存在黏膜来源。在无S9的鼠伤寒沙门氏菌TA98菌株中，无菌大鼠尿液（1144±64回复突变体/毫升）的致突变性低于定殖化动物尿液（1467±171回复突变体/毫升）。在有S9存在的情况下，定殖化动物尿液（894±56回复突变体/毫升）的致突变性高于无菌大鼠尿液（686±60回复突变体/毫升）。肠道菌群的存在在2,6 - DNT的活化中起重要作用，但也存在其他代谢途径，如小肠黏膜和/或肝脏酶，它们可产生排泄性遗传毒性物质。
