NITROREDUCTION AND FORMATION OF HEMOGLOBIN ADDUCTS IN RATS WITH A HUMAN INTESTINAL MICROFLORA

In the covalent binding of nitroarenes to macromolecules, nitroreducti on is an important step. The intestinal microflora represents an enorm ous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administered nitroarenes is prima rily located in the intestine. in this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in fem ale Wistar rats. Germ-free (GF) rats were equipped with a bacterial fl ora derived from human feces. Nontreated GF rats and GF animals equipp ed with a conventional rat flora were used as controls. The compositio n of the human and the conventional microflora isolated from the rats were consistent with the microflora of the administered feces. In the rats receiving only sunflower seed oil, no adducts were detected. The animals equipped with a human or rat microflora that received 2-aminof luorene (2-AF) formed 2-AF hemoglobin (Hb)-adducts at average levels ( mean +/- SEM) of 5.3 +/- 0.3 and 6.7 +/- 0.7 mu mole/g Hb, respectivel y. After 2-NF administration, the adduct levels were 0.022 +/- 0.003 a cid 0.043 +/- 0.010 mu mole/g Hb, respectively. In the GF rats, an add uct level of 0.57 +/- 0.09 was determined after 2-AF administration an d no adducts were detected after 2-NF administration. The results show that nitroreduction by an acquired human intestinal microflora and su bsequent adduct formation can be studied in the rat in vivo.