Induction of liver preneoplastic lesions by aminophenylnorharman, formed from norharman and aniline, in male F344 rats.
9-(4'-Aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorharman, APNH), produced by the reaction of norharman with aniline in the presence of S9 mix, is a novel heterocyclic amine (HCA), with mutagenicity to Salmonella typhimurium TA 98 and YG 1024 comparable to that of other HCAs such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). This experiment was designed to investigate its potential to induce glutathione S-transferase placental form (GST-P) positive foci in the liver. Male F344 rats, 7 weeks old, were fed diet containing 0, 10, 20, or 50 ppm APNH for 4 weeks, killed by ether euthanasia and performed complete necropsy. Numbers of GST-P positive foci larger than 0.1 mm in diameter induced by APNH at the dose of 10, 20, and 50 ppm were increased in a dose dependent manner to 0.52, 1.3, and 21 foci/cm2, respectively, with areas of 0.006, 0.01, and 2.3 mm2/cm2. No such GST-P positive foci were observed in rats fed control diet. These findings suggest that APNH has hepatocarcinogenic potential in male F344 rats.
Kawamori
T
T
Cancer Prevention Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. tkawamor@gan2.ncc.go.jp
Totsuka
Y
Y
Ishihara
J
J
Uchiya
N
N
Sugimura
T
T
Wakabayashi
K
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000378:metabolism*; D007211:Indoles / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D014408:Biomarkers, Tumor; D002273:Carcinogens; D007211:Indoles; D011725:Pyridines; D005982:Glutathione Transferase; C421010:9-(4'-aminophenyl)-9H-pyrido(3,4-b)indole