Abstract
The arylamine carcinogens aminofluorene, α-naphthylamine, β-naphthylamine, benzidine and methylene bis-2-chloroaniline are acetylated by the same polymorphic N-acetyltransferase (EC 2.3.1.5) as isoniazid and sulfamethazine in human and rabbit populations. Apparent Km values for these carcinogens determined with human and rabbit N-acetyl-transferases obtained from rapid and slow isoniazid acetylator individuals are approximately one order of magnitude smaller than for the polymorphic drug substrate, sulfamethazine. The apparent Km values for all the carcinogens and sulfamethazine were also strongly correlated with their octanol-water partition coefficients indicating that their kinetic properties are highly dependent upon their hydrophobic nature. Since differences in susceptibility to toxicity from isoniazid, hydralazine and procainamide are associated with different acetylator phenotypes, the possibility is raised that rapid and slow isoniazid acetylator populations may differ in susceptibility to chemical carcinogenicity from exposure to arylamines.
- Copyright © 1978 by Academic Press, Inc.
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