Comparative study on metabolic formation of N-arylformamides and N-arylacetamides from carcinogenic arylamines in mammalian species.
The metabolism of carcinogenic arylamines was examined focusing on their N-acylation in mammalian species. When 4-aminobiphenyl, 2-aminonaphthalene, 2-aminofluorene, or 1-aminopyrene was given orally to rabbits, the corresponding N-arylformamides were isolated from the urine together with the corresponding N-arylacetamides. Identification of these N-arylformamides and N-arylacetamides was performed unequivocally by comparing their mass and UV spectra, and thin-layer chromatographic behaviors with those of authentic samples. Such metabolic conversion of the arylamines to the N-arylformamides and N-arylacetamides was also observed in guinea pigs and rats. In addition, carcinogenic nitro compounds such as 4-nitrobiphenyl and 2-nitronaphthalene, which are metabolically reducible to the arylamines, were metabolized to the corresponding N-arylformamides and N-arylacetamides in rabbits. On the other hand, quantitative experiments showed that only minor amounts of the N-arylformamides and N-arylacetamides were excreted in the urine or feces of rats and rabbits given the arylamines. This seems to be due to almost complete further metabolism of these N-acyl derivatives in vivo. Liver cytosols from several mammalian species exhibited a significant N-formylating activity toward the arylamines in the presence of N-formyl-L-kynurenine and N-acetylating activity in the presence of acetyl-CoA. In rabbits, the N-formylating activity was clearly higher than the N-acetylating activity, while the reverse was the case in guinea pigs and hamsters. The experiments with rat liver preparations showed that the liver cytosolic N-formylating and N-acetylating activities are due to formamidase and arylamine acetyltransferase, respectively. Furthermore, enzymatic transfer of the formyl group from one arylamine to another was demonstrated.