THE ABILITY OF 2 COOKED FOOD MUTAGENS TO INDUCE ABERRANT CRYPT FOCI IN MICE

The aberrant crypt foci assay has been used extensively to study diffe rent compounds for chemopreventive action, but almost all investigatio ns 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]quin oline (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, T wo additional groups were given azoxymethane (AOM) (5 mg/kg body weigh t) and 1,2-dimethylhydrazine dihydrochloride (DMH-2HCI) (20 mg/kg body weight), respectively, one dose a week for two weeks, Animals were ki lled after four and 10 weeks, After four weeks only the mice dosed wit h IQ and PhIP had aberrant crypt foci, A much higher number of aberran t 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 less than or e qual to 0.001) small and total aberrant crypt foci than the other grou ps, AOM and DMH induced a higher percentage of medium or large sized a berrant crypt foci than PhIP or IQ, The interpretation of the aberrant crypt foci as precursor lesions for colon cancer in the PhIP and IQ m ice is difficult because PhIP and IQ have not been reported to be colo nic 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 ma y be preferable.