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Comparative Study on Metabolic Formation of N-Arylformamides and 3 N-Aryl-acetamides from Carcinogenic Arylamines in Mammalian Species¹

Institute of Pharmaceutical Science, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734, Japan

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. Identifiation 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.

¹ This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture, Japan.

² To whom requests for reprints should be addressed.

³ Present address: Wakunaga Pharmaceutical Co., Ltd., 1624 Koda-cho, Takada-gun, Hiroshima 729-64, Japan.

⁴ Present address: Santen Pharmaceutical Co., Ltd., 3-9-19 Shimoshinjyo, Higashiyodogawa-ku, Osaka 533, Japan.

Received 3/20/87. Revised 8/30/88. Revised 1/ 6/89. Accepted 1/16/89.

This article has been cited by other articles:

				O. Ueda, S. Kitamura, and S. Ohta Deacylation of N-Arylformamides and N-Arylacetamides by Formamidase in Rat Liver Drug Metab. Dispos., December 1, 2002; 30(12): 1297 - 1299. [Abstract] [Full Text] [PDF]