Activation of mutagenic and carcinogenic heterocyclic amines by S-9 from the liver of a rhesus monkey

Abstract

The mutagenicity of a series of heterocyclic amines isolated from various cooked foods and from pyrolysates of amino acids and protein was assayed in Salmonella typhimurium TA98 in the presence of an S-9 fraction prepared from the liver of an untreated male rhesus monkey ( Macaca mulatta). All the compounds showed mutagenicity, which ranged from 1 to 2500 revertants/μg chemical/mg S-9 protein. 2-Amino-3,4-dimethylimidazo[4,5- f]quinoline (MeIQ) showed the highest specific mutagenic activity, followed by 2-amino-3,7,8-trimethylimidazo[4,5- f]quinoxaline (7,8-DiMeIQx), 2-amino-3-methylimidazo[4,5- f]quinoline (IQ), 2-amino-3,4,8-trimethylimidazo[4,5- f]quinoxaline 4,8-DiMeIQx, 3-amino-1-methyl-5 H-pyrido[4,3- b]indole (Trp-P-2), 3-amino-1,4-dimethyl-5 H-pyrido[4,3- b]indole (Trp-P-1), 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx), 2-amino-6-methyldipyrido[1,2- a:3′,2′- d]imidazole (Glu-P-1) and 2-amino-3-methyl-9 H-pyrido[2,3- b]indole (MeAαC). 2-Amino-9 H-pyrido[2,3- b]indole (AαC) and 2-aminodipyrido[1,2- a:3′,2′- d]imidazole (Glu-P-2) also showed definite but weak mutagenicity. When compared with previously reported data, these specific mutagenic activities were very close to those of some heterocyclic amines assayed with the S-9 of human liver, slightly lower than those determined with the S-9 of untreated rat liver and much lower than those determined with S-9 from the liver of the untreated hamster or mouse. Most of the heterocyclic amines tested in this experiment have shown carcinogenicity in mice and rats. The experimental results now reported suggest the possible carcinogenicity of these heterocyclic amines in primates as well, including humans.