Fate and distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in mice at a human dietary equivalent dose.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine rodent carcinogen that is found at the ppb level in cooked meat. Most laboratory studies are at 10(4)-10(7)-fold greater concentrations than actual ingested human doses. We report the first study of the bioavailability and fate of this heterocyclic amine at a human dietary equivalent dose using the high sensitivity offered by accelerator mass spectrometry. [2-14C]PhIP was administered to C57BL/6 male mice (41 ng/kg) by gavage. Tissues and excreta were collected over the subsequent 96 h. One hundred % of the administered dose was excreted in urine (90%) and feces (10%) over the length of the study. Absorption of the radiocarbon-tagged PhIP from the gastrointestinal tract was rapid, with radiocarbon levels peaking in the whole blood and urine within 1 h of exposure. Fecal 14C levels peaked at 12 h. Tissue levels peaked by 3 h with the highest concentrations of radiolabel in the intestine, stomach, and liver, followed by the kidney, pancreas, lung, and spleen. Low levels of 14C from PhIP (0.01-0.04% of the administered dose) could be detected in the tissues 48-96 h after exposure, possibly due to covalent binding to protein or DNA. The calculated half-life of PhIP at this dose was 1.14 h. This study is the first example of how accelerator mass spectrometry can be used to gather biological information about carcinogenic compounds at environmental levels of exposure.
Turteltaub
K W
KW
Biomedical Sciences Division, Lawrence Livermore National Laboratory, Livermore, California 94550.
Vogel
J S
JS
Frantz
C E
CE
Shen
N
N
D000818:Animals; D005243:Feces; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine