Disposition of benzo[c] fluorene in rats
Résumé
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants and food contaminants. Some of them are mutagenic/genotoxic and have shown clear carcinogenic effects in mammals. Among the PAHs found in food commodities, benzo[c]fluorene (B[c]F) was demonstrated to be carcinogenic in rodents and the occurrence of corresponding pulmonary adducts has been demonstrated, suggesting a bioactivation pathway. B[c]F distribution and biotransformation was studied in rats given a single oral dose of radiolabelled B[c]F (0.64 or 640 μg/kg body weight). At intervals of 2, 4, 6, 8, 12, 24 and 48 h thereafter, animals were sacrificed, excreta were collected and various tissues were sampled. Radioactivity was measured in all samples before extraction with dichloromethane/methanol mixtures. Metabolic profiles were performed by radio-HPLC and metabolites were analyzed by LC–MS/MS. Results shown that B[c]F was extensively absorbed and biotransformed in rats. The metabolic balance at 48 h indicates that 8–10% of the radioactivity was eliminated in urine while 55–69% was found in faeces, depending on administered dose. The major part of fecal radioactivity corresponded to unchanged B[c]F, whereas analysis of urine samples revealed only polar metabolites (mainly glucurono- and sulfo-conjugates of mono-, di-, tri- and tetra-hydroxylated B[c]F). The highest concentrations of radioactivity in tissues were found in liver, irrespective of the administered dose, the highest values being recovered 2 h post dosing. The characterization of the metabolic pathways of BcF in rat is in progress, with the objective to identify reactive metabolites and to better understand the mechanisms of genotoxicity of this contaminant.