The metabolic basis for inhibitory effects in chemical carcinogenesis by arylamines

The inhibition of the carcinogenicity of N-2-fluorenylacetamide (2-FAA) by acetanilide (AA), p-hydroxyacetanilide (p-OH-AA), butylated hydroxytoluene (BHT), and chloramphenicol is reviewed. The mechanisms of action by which inhibition may occur are as follows: 1) inhibition of the binding of the activated metabolite of FAA to cellular macromolecules (DNA, RNA, and proteins), 2) changes in the amount of the N-hydroxylated metabolite, believed to be the first step of activation of FAA, formed and excreted in the urine, 3) induction of the enzyme glucuronyl transferase which increases the formation of glucosiduronic acid that results in a rapid excretion of the carcinogens, 4) depletion of sulfate by p-OH-AA, the major metabolite of AA. The sulfate ion is required for the second activation step, i.e., the formation of the sulfate ester of N-OH-FAA. The data show several of the inhibitors may operate by one or more of the above mechanisms of inhibition.