LOW-LEVEL BIOLOGICAL DOSIMETRY OF HETEROCYCLIC AMINE CARCINOGENS ISOLATED FROM COOKED FOOD

The bioavailability and the bioreactivity of the carcinogenic heterocy clic amine 14]2-amino-1-methyl-6-phenyl-imidazo[4,5b]pyridine (PhIP) h ave been investigated at a dose approximating that likely from the hum an diet by accelerator mass spectrometry (AMS). 12-C-14]PhIP was admin istered to mice at a dose equivalent to the consumption of two 100 g b eef patties (41 ng/kg). The biological half-life of PhIP was 1 hr, wit h 90% of the dose being excreted via the urine. Peak tissue PhIP conce ntrations were reached within 3 hr, with the highest levels in the tis sues of the gastrointestinal tract, followed by the liver, kidney, pan creas, and thymus. Since the detection limit by AMS is dependent on th e natural abundance of C-14, we have achieved further increases in sen sitivity by producing mice that have 20% of the natural abundance of C -14. Use of these C-14-depleted animals allows measurements to be made near the natural level of exposure for many environmental carcinogens . PhIP-DNA adduct levels have also been measured by P-32-postlabeling at doses of 1.0, 10, and 20 mg/kg. The highest adduct levels were foun d in the pancreas, thymus, heart, and liver and increased linearly wit h dose. The principal adducts are derived from guanine.