Carcinogenicity of a mutagenic compound from food, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C), in male F344 rats.
Carcinogenicity of 2-amino-3-methyl-9H-pyrido[2,3-b]-indole (MeA alpha C) was investigated at dietary levels of 0 (control), 0.01, 0.02, 0.04 and 0.08% using male F344/DuCrj rats. The administration of MeA alpha C was continued for 100 experimental weeks for the control, 0.01 and 0.02% groups, but halted after 52 and 26 experimental weeks for the 0.04 and 0.08% groups respectively due to severe toxicity. Well-differentiated hepatocellular carcinomas, lacking in control animals, were induced in 5/20 rats (25%) and 6/20 rats (30%) of the 0.01% and 0.02% groups respectively. Pancreatic acinar cell adenomas were also significantly increased in the 0.01% (30%) and 0.02% (40%) groups, in association with high incidences of hyperplastic lesions of acinar cells. Fibromas in the subcutis developed at a high incidence (70%) in the 0.02% group. MeA alpha C was also suggested to elicit fibrosarcomas in the salivary gland and transitional cell carcinomas in the urinary bladder. Among the non-neoplastic lesions, severe atrophy of the salivary glands and pancreas and severe renal toxicity were noteworthy. In conclusion, MeA alpha C is a multi-targeting carcinogen in rats, similar in this respect to other heterocyclic amines.
Tamano
S
S
First Department of Pathology, Nagoya City University Medical School, Japan.
Hasegawa
R
R
Hagiwara
A
A
Nagao
M
M
Sugimura
T
T
Ito
N
N
D000410:Alanine Transaminase / Q000097:blood; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002243:Carbolines / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005502:Food; D008099:Liver / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D010190:Pancreatic Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D012469:Salivary Glands / Q000187:drug effects / Q000201:enzymology
D002243:Carbolines; D002273:Carcinogens; D009153:Mutagens; C017821:2-amino-3-methyl-9H-pyrido(2,3-b)indole; D000410:Alanine Transaminase; D000681:Amylases