Low-dose-dependent carcinogenic potential of 2-amino-3-methylimidazo[4,5-f]quinoline in the immunodeficient (SCID) mouse colon.
The carcinogenic potential of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), one of the most potent mutagenic heterocyclic aromatic amines in food, for the colon was assessed in mice with severe combined immunodeficiency (SCID). In Experiment I, 60 male animals, 7-8 weeks old, were administered 300, 100, or 0 ppm IQ in the diet for 20 weeks. The incidence of aberrant crypt foci (ACF), preneoplastic lesions, was 100% in the two IQ-administered groups, whereas no ACF were found in the controls. Larger lesions, at least four aberrant crypts per focus, were noted in the colons of both treated groups. Most ACF were located in the proximal colon, and the bromodeoxyuridine-labeling indexes were elevated in a dose-dependent manner, especially in this region. In Experiment II, IQ was administered in the diet at 50, 10, 2, or 0 ppm to 60 female and male 7- to 8-week-old SCID mice for 30 and 23 weeks, respectively. The incidence of ACF was dose dependent in both sexes: 100%, 100%, and 63% in the females administered 50, 10, and 2 ppm, respectively, and 100%, 83%, and 38%, respectively, in the males. Lesions of at least four aberrant crypts per focus were again evident with the 50-ppm dose. The long-term or higher dose administration of IQ in the diet might thus be applied to elucidate colon carcinogenesis in the SCID mouse.
Salim
E I
EI
First Department of Pathology, Osaka City University Medical School, Japan.
Wanibuchi
H
H
Yamamoto
S
S
Morimura
K
K
Mori
S
S
Makino
S
S
Nomura
T
T
Fukushima
S
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009929:Organ Size / Q000187:drug effects; D011804:Quinolines / Q000633:toxicity*; D016511:Severe Combined Immunodeficiency
D002273:Carcinogens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D001973:Bromodeoxyuridine