Ae. Director et al., CYTOGENETIC ANALYSIS OF MICE CHRONICALLY FED THE FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5B]PYRIDINE, Mutation research. Section on environmental mutagenesis and related subjects, 359(1), 1996, pp. 53-61
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.