Organ differences in the enhancing potential of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine on carcinogenicity in the prostate, colon and pancreas.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant carcinogenic heterocyclic amine in cooked meat and fish, is speculated to be associated with human carcinogenesis. It has been shown to induce DNA adducts in a variety of organs in rodents and thus clarification of any enhancement of neoplasia is a very important subject for assessing human risk. In order to evaluate modifying effects of PhIP on carcinogenesis, several in vivo experiments in rats were performed. These featured dietary administration of PhIP at different dose levels and for different durations, and included intragastric dosing for a short period, or continuous dietary administration after initiation with other carcinogen, namely 3,2'-dimethyl-4-aminobiphenyl (DMAB) or 1,2-dimethylhydrazine (DMH). The data indicate that a short administration of PhIP is sufficient to induce prostate tumors but long-term treatment is required for effects in the colon. They also suggest tumor enhancing potential dependent on the organ, i.e. evident in the colon but not the prostate. Furthermore, promotion of colon neoplasia may depend on the initiator employed. Thus these findings suggest that the carcinogenic mechanisms of PhIP may vary in its different target organs.
D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000611:Aminobiphenyl Compounds / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003106:Colon / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000139:chemically induced; D018736:DNA Adducts / Q000378:metabolism; D004357:Drug Synergism; D007093:Imidazoles / Q000633:toxicity*; D008297:Male; D009928:Organ Specificity; D010179:Pancreas / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000139:chemically induced; D011467:Prostate / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; C001042:2',3-dimethyl-4-aminobiphenyl; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019813:1,2-Dimethylhydrazine