Carcinogenic effect of the simultaneous administration of five heterocyclic amines to F344 rats

F344 rats were given five mutagenic and carcinogenic heterocyclic amines, i.e., 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 2-amino-9H-pyrido[2,3-b]indole (AaC), and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), mixed together in the diet each at one-fifth of the concentration used in the previous single-compound carcinogenesis experiment. Liver, colon and Zymbal gland tumors in both sexes, skin tumors in males and clitoral gland tumors in females were induced at significantly higher incidences than in control groups. Among them, the incidences of liver tumors in both sexes, skin tumors in males and clitoral gland tumors in females were significantly higher than those expected from the simple assumptions that the incidence of tumors induced by each compound would be one-fifth of that in the corresponding previous experiment and that the combined effect of the five chemicals would be additive.