Role of the Intestinal Microbiota in the Activation of the Promutagen 2,6-dinitrotoluene to Mutagenic Urine Metabolites and Comparison of GI Enzyme Activities in Germ-free and Conventionalized Male Fischer 344 Rats

摘要

After male germ-free and conventionalized Fischer 344 rats were administered peros (p.o.) 75 mg/kg 2,6-DNT, intestinal nitroreductase, beta-flucuronidase, 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 couterparts. This indicated a potential mucosal source for the enzymes. Urines from germ-free rats were less mutagenic than those from conventionalized animals in Salmonella typhimurium strain TA98 without S9. In the presence of S9, urine from conventionalized animals was more mutagenic than that from germ-free rats. 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.