Contribution of intestinal microfloral metabolism to the total macromolecular covalent binding of 1-nitropyrene in the lung and liver of the rat

Abstract

1-Nitropyrene (NP) is a direct acting mutagen found in diesel exhaust and coal-combustion fly ash. The purpose of this study was to investigate the contribution of gut microfloral metabolism to the macromolecular covalent binding (MCB) of NP and/or its metabolites in lungs and liver of the rat. Normal and antibiotic treated rats were administered [ 14C]NP and MCB was quantitated at various times in lungs and livers. Abolition of gut microfloral metabolism by antibiotic treatment significantly altered total MCB in lungs. MCB in lungs of antibiotic-treated animals 4 h after oral administration of NP was 0.15 nmol NP equivalents/g and was significantly ( P < 0.05) decreased to less than one-half of control values (0.42 nmol NP equivalents/g). MCB in lungs of antibiotic-treated rats was no different from the controls 1 week after NP administration (0.1 nmol NP equivalents/g). Comparison of livers from control and antibiotic-treated rats demonstrated the same pattern of MCB as lungs but differences were not significant. These results reveal that metabolism by gut microflora may play a role in the activation and covalent binding of NP to macromolecules. However, the alteration of covalent binding observed after antibiotic treatment was a change in the time course of formation and breakdown of covalently bound forms and not an effect on the quantity of bound material remaining at 1 week indicating that gut microfloral metabolism is not an exclusive pathway for bioactivation of NP in the rat.