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
| Autor: | R. W. Chadwick, Ronald Williams, J. C. Allison, Jerjang Chang, M. J. Kohan, S. E. George |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Cancer Research Biology Reductase Cecum Nitroreductase Intestine Small medicine Animals Germ-Free Life Toxicokinetics Large intestine Intestine Large Intestinal Mucosa Biotransformation Carcinogen Glucuronidase chemistry.chemical_classification Mutagenicity Tests Nitroreductases Molecular biology Rats Inbred F344 Rats Intestines Dinitrobenzenes medicine.anatomical_structure Enzyme Oncology Biochemistry chemistry Toxicity |
| Zdroj: | Cancer Letters. 79:181-187 |
| ISSN: | 0304-3835 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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