Chromosome aberrations induced in mice by chronic feeding of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ).
Dietary intake of mutagenic compounds is considered to be an important factor for the induction of some human cancers. Highly mutagenic compounds are known to be formed in meat during the cooking process. Since the discovery of such compounds, many studies have been conducted to evaluate their carcinogenic potential. One of the most mutagenic compounds formed in the cooking of meat is 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). The recent development of mouse chromosome painting probes expand the capability of evaluating these food mutagens as potential clastogens in vivo. In this paper, we demonstrate the induction of chromosome aberrations in mice chronically exposed to MeIQ in their diet. CDF1 female mice were fed 400 ppm MeIQ beginning at 7 wk of age. At 76 wk of age, five control and eight exposed mice were euthanized. Blood and bone marrow cells were obtained and arrested in metaphase. Whole chromosome painting probes were used for fluorescence in situ hybridization of metaphase cells from blood and bone marrow. MeIQ-exposed mice were found to have a twofold increase in translocations and a 16-fold increase in fragments in their peripheral blood compared with controls. No aberrations were observed in the bone marrow. All organs were examined for the presence of tumours and routine histopathological analysis was performed on all organs as well as any tissue with macroscopic abnormalities. Forestomach and/or liver tumours developed in all but one of the mice fed MeIQ, but no such tumours were observed in the control mice. These data indicate that MeIQ is clastogenic and carcinogenic in vivo.
Ramsey
M J
MJ
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94551, USA.
Nagao
M
M
Inoue
R
R
Fujita
H
H
Matsushima
T
T
Tucker
J D
JD
D000821:Animal Feed; D000818:Animals; D001773:Blood Cells / Q000187:drug effects / Q000648:ultrastructure; D001854:Bone Marrow Cells / Q000187:drug effects / Q000648:ultrastructure; D002273:Carcinogens / Q000633:toxicity*; D002869:Chromosome Aberrations; D003296:Cooking; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008461:Meat Products; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D013274:Stomach Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D009153:Mutagens; D011804:Quinolines; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline