Formation, metabolic activation by N, O-acyltransfer, and hydrolysis of N-acyl-N-arylamine derivatives.
Amines and hydroxylamines can be produced from N-substituted aryl compounds by many organisms. Both functional groups can by N-acetylated enzymatically be preparations from the tissues of most mammalian species. The N-acylated products are subject to further metabolism including oxidation, hydrolysis, conjugation, or, with arylhydroxamic acids, N-O-acyltransfer. These reactions are of concern because they lead to changes in the levels of compounds that can alter tissue macromolecules. Select N-hydroxyarylamines and N-acyloxyarylamines can react with nucleic acid, and the hydroxylamines are mutagenic in bacterial systems. Thus the relative rates of these biochemical reactions within an organism may determine whether exposure to an arylamine will cause an adverse biologic effect. The ability of an arylamine to induce tumors reflects the composite effects of genetic determinants (i.e., species, strain, sex, and organ) as well as exposure to xenobiotic compounds because these factors modulate the metabolic pathways crucial to the carcinogenic process. The extreme genetic differences in the levels of the enzymes involved in the metabolism of N-acyl derivatives of arylamines in man and experimental animals offers an experimental approach that may aid in elucidating the mechanisms by which these compounds induce cancer.
D000123:Acetyltransferases / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism*; D000588:Amines / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D006801:Humans; D006898:Hydroxylamines / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D009928:Organ Specificity; D011817:Rabbits; D013045:Species Specificity
D000588:Amines; D002273:Carcinogens; D006898:Hydroxylamines; D000217:Acyltransferases; D000123:Acetyltransferases