Low-level biological dosimetry of heterocyclic amine carcinogens isolated from cooked food

The bioavailability and the bioreactivity of the carcinogenic heterocyclic amine [2-¹⁴C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) have been investigated at a dose approximating that likely from the human diet by accelerator mass spectrometry (AMS). [2-¹⁴C]PhIP was administered to mice at a dose equivalent to the consumption of two 100 g beef patties (41 ng/kg). The biological half-life of PhIP was 1 hr, with 90% of the dose being excreted via the urine. Peak tissue PhIP concentrations were reached within 3 hr, with the highest levels in the tissues of the gastrointestinal tract, followed by the liver, kidney, pancreas, and thymus. Since the detection limit by AMS is dependent on the natural abundance of ¹⁴C, we have achieved further increases in sensitivity by producing mice that have 20% of the natural abundance of ¹⁴C. Use of these ¹⁴C-depleted animals allows measurements to he made near the natural level of exposure for many environmental carcinogens PhIP-DNA adduct levels have also been measured by ³²P-postlabeling at doses of 1.0, 10, and 20 mg/kg. The highest adduct levels were found in the pancreas, thymus, heart, and liver and increased linearly with dose. The principal adducts are derived from guanine.