Comparison of initiation potential of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in an in vivo carcinogen bioassay system.
A new approach to low-dose assessment of carcinogenic potential was applied to food contaminant pyrolysis products. Single intragastric doses of the carcinogenic pyrolysates, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline MeIQx), were given 12 h after two-thirds partial hepatectomy (PH) to F344 male rats. Two weeks thereafter the animals were placed on a basal diet containing 0.05% phenobarbital (PB) for 6 weeks combined with an i.p. administration of D-galactosamine (300 mg/kg) to facilitate growth of initiated cells. Both IQ and MeIQx clearly caused initiation of hepatocarcinogenesis as revealed by induction of preneoplastic placental-form glutathione-S-transferase-positive (GST-P+) hepatocyte foci composed of more than three cells (approximately 30 microns in diameter). A similar protocol without performance of PH before pyrolysate administration gave a positive result only for the IQ-treated group indicating that cell proliferation is essential during the low-dose, one-shot initiation step. IQ was found to be two to three times more potent in inducing GST-P+ foci using both protocols. The current approach could find application in practical carcinogenicity screening of chemicals, for which only small amounts are available.
Tsuda
H
H
First Department of Pathology, Nagoya City University Medical School, Japan.
Takahashi
S
S
Yamaguchi
S
S
Ozaki
K
K
Ito
N
N
D000818:Animals; D001835:Body Weight; D015197:Carcinogenicity Tests; D002273:Carcinogens; D004790:Enzyme Induction; D005688:Galactosamine / Q000633:toxicity; D005982:Glutathione Transferase / Q000096:biosynthesis; D006498:Hepatectomy; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size; D010634:Phenobarbital / Q000633:toxicity; D011804:Quinolines / Q000633:toxicity*; D011810:Quinoxalines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D009153:Mutagens; D011804:Quinolines; D011810:Quinoxalines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D005688:Galactosamine; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D005982:Glutathione Transferase; D010634:Phenobarbital