The ability of two cooked food mutagens to induce aberrant crypt foci in mice.
The aberrant crypt foci assay has been used extensively to study different compounds for chemopreventive action, but almost all investigations have used initiators not normally found in the diet. In the present study two food-borne initiators, 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were used. To simulate the human exposure further, we chose a feeding regimen with continuous low IQ- and PhIP-doses. Throughout the study female mice were given diets with or without 0.03% IQ or 0.03% PhIP. Two additional groups were given azoxymethane (AOM) (5 mg/kg body weight) and 1,2-dimethylhydrazine dihydrochloride (DMH-2HCl) (20 mg/kg body weight), respectively, one dose a week for two weeks. Animals were killed after four and 10 weeks. After four weeks only the mice dosed with IQ and PhIP had aberrant crypt foci. A much higher number of aberrant crypt foci were found in the IQ mice (31.8 +/- 5.2) than in the PhIP mice (0.5 +/- 0.3). After 10 weeks aberrant crypt foci were found in all dosed groups. The IQ mice had significantly more (P < or = 0.001) small and total aberrant crypt foci than the other groups. AOM and DMH induced a higher percentage of medium or large sized aberrant crypt foci than PhIP or IQ. The interpretation of the aberrant crypt foci as precursor lesions for colon cancer in the PhIP and IQ mice is difficult because PhIP and IQ have not been reported to be colonic carcinogens. If cooked food mutagens such as IQ or PhIP are to be used as initiators in the aberrant crypt foci test, the use of rats may be preferable.
Kristiansen
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E
Institute of Toxicology, National Food Agency, Soborg, Denmark.
Meyer
O
O
Thorup
I
I
D000704:Analysis of Variance; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003296:Cooking; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000633:toxicity; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D005527:Food, Fortified; D006358:Hot Temperature / Q000009:adverse effects*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000633:toxicity*; D011810:Quinoxalines / Q000633:toxicity*; D012016:Reference Values; D015430:Weight Gain / Q000187:drug effects
D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; D011810:Quinoxalines; C078255:N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D003849:Deoxyguanosine; D001397:Azoxymethane