Comparative carcinogenicity of 4-aminobiphenyl and the food pyrolysates, Glu-P-1, IQ, PhIP, and MeIQx in the neonatal B6C3F1 male mouse.
The tumorigenic activities of four representative heterocyclic amine food pyrolysates, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), were assessed in the neonatal male B6C3F1 mouse and were compared with that of the potent human carcinogen, 4-amino-biphenyl (4-ABP). These aromatic amines were administered by i.p. injection at two dose levels on days 1, 8, and 15 after birth; and the incidence of tumors was examined at 8 and 12 months. Glu-P-1, IQ, PhIP, MeIQx, and 4-ABP each induced a significant incidence of hepatic adenomas, as compared to the solvent-treated (DMSO) control. Hepatocellular carcinomas were also observed with 4-ABP, SO, and MeIQx. Overall tumorigenicity was in the order: 4-ABP greater than Glu-P-1 greater than IQ approximately PhIP greater than MeIQx greater than DMSO. In the neonatal B6C3F1 mouse, these heterocyclic aromatic amines showed potent tumorigenicity after 8 and 12 months at total doses that were 5-10,000-fold less than those employed in standard chronic bioassays.
Dooley
K L
KL
National Center for Toxicological Research, Jefferson, AR 72079.
Von Tungeln
L S
LS
Bucci
T
T
Fu
P P
PP
Kadlubar
F F
FF
D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D007093:Imidazoles / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D011810:Quinoxalines / Q000633:toxicity*
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; D011810:Quinoxalines; C006757:4-biphenylamine; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine