Carcinogenicity of the N-hydroxy derivative of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline and 3,2′-dimethyl-4-aminobiphenyl in the rat

Heterocyclic amines and carcinogenic aromatic amines are similarly metabolically activated suggesting that they may have similar organ specificity. Three day-old male ACI/seg rats were injected, i.p., twice a week for 10 weeks with 50 μmol/kg of N-hydroxy-3,2′-dimethyl-4-aminobiphenyl (N-OH-DMABP; Group II), N-OH-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-OH-MeIQx; Group III) or N-OH-2-amino-1-methyl-6-phenylimidaza-[4,5-b]pyridine (N-OH-PhIP; Group IV). Animals in control group (Group I) were similarly injected with solvent alone. The animals were sacrificed at age 68 weeks, and 31, 30, 27 and 31 rats from Groups I, II, III and IV, respectively, were evaluated. Colon carcinomas were found in 0, 15 (P<0.001), 2 and 4 (P<0.06), and bladder transitional cell tumors in zero, two, two and four (P<0.06), in Group I, II, III and IV, respectively. The incidence of atypical hyperplasia of ventral prostate in Groups III and IV, and of anterior prostate and seminal vesicle in all treated groups was also significantly greater (P<0.05). These results suggest that N-OH-PhIP and N-OH-MeIQx may be potential carcinogens for the prostate. Since bladder tumor is rare in ACI rats, N-OH-PhIP may also be a potential carcinogen for the bladder.