Contribution of intestinal microfloral metabolism to the total macromolecular covalent binding of 1-nitro-pyrene in the lung and liver of the rat.
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 less than 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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000378:metabolism*; D002250:Carbon Radioisotopes; D007422:Intestines / Q000382:microbiology*; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D011721:Pyrenes / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D046911:Macromolecular Substances; D011721:Pyrenes; C004482:1-aminopyrene; C032668:1-nitropyrene