CYTOGENETIC ANALYSIS OF MICE CHRONICALLY FED THE FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5B]PYRIDINE

The cytogenetic effects in mice chronically fed the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) were evaluated by chromosome painting, micronucleated normochromatic erythrocytes (MN NCEs) and sister chromatid exchanges (SCEs), PhIP and numerous other heterocyclic amines have been isolated from cooked foods, and many hav e been found to be carcinogenic in laboratory rodents, Female C57BL/6N mice were chronically fed a diet containing 0, 100, 250 or 400 ppm of PhIP beginning at 8 weeks of age, Peripheral blood and bone marrow we re taken from 5 mice per treatment group at 1, 4 and 6 months from the start of exposure, PhIP was removed from the diet for a final month o f the experiment, at which time blood was taken from the remaining ani mals. Chromosome-specific composite DNA probes for mouse chromosomes 2 and 8 were hybridized to metaphase cells from each tissue. The 1- and 4-month time points showed no statistically significant difference be tween the control and exposed mice for either tissue in chromosome abe rration frequencies, Both MN NCEs and SCEs were analyzed at a single t ime point during exposure (4 months for MN NCEs and 6 months for SCEs) and again 1 month after removing PhIP from the diet. MN NCEs in the p eripheral blood showed a statistically significant dose response, with all values decreasing significantly 1 month after removing PhIP from the diet. SCE frequencies in the peripheral blood showed an approximat e doubling compared to control mice, and decreased to control levels 1 month after removing PhIP from the diet. SCE frequencies in the bone marrow of exposed mice showed no difference from the control animals, These results show that chronic ingestion of PhIP by female C57BL/6 mi ce does nor produce persistent cytogenetic damage as visualized by chr omosome aberrations, MN NCEs or SCEs.