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.
Tatsumi
K
K
Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan.
Kitamura
S
S
Amano
H
H
Ueda
K
K
D015081:2-Naphthylamine / Q000378:metabolism*; D000215:Acylation; D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D005449:Fluorenes / Q000378:metabolism*; D006168:Guinea Pigs; D006868:Hydrolysis; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051379:Mice; D009281:Naphthalenes / Q000378:metabolism*; D011721:Pyrenes / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D005449:Fluorenes; D009281:Naphthalenes; D011721:Pyrenes; C006757:4-biphenylamine; C012177:2-aminofluorene; D015081:2-Naphthylamine; C004482:1-aminopyrene