Fate and distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats.
Fischer 344 rats were given a single dose of 0.60 mg/animal of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by gavage; and radioactivity contained in feces, urine, blood, serum proteins, hemoglobin, and tissues was determined at 12, 24, 48 and 96 h after dosing. One major and four minor radioactivity-containing fractions were found in the urine and one major and two minor radioactivity-containing fractions were found in the feces. The feces was the major route of excretion, representing 78% of dose during the first 24 h, and unchanged PhIP in the feces accounted for 51% of the dose. Unmetabolized PhIP was also shown to be the major radioactive fraction in bile and feces from animals given a single dose by i.p. injection. Blood contained a small fraction of the dose and the major, persistently-bound form of PhIP in the blood was to hemoglobin. At 12 h after administration of the dose the colon and cecum contained the highest concentration of radioactivity, while at later times the kidney and liver showed the highest concentration. Of the tissue-contained radioactivity 80-90% was ethanol insoluble at time points later than 24 h, suggesting that it was covalently bound to macromolecules.
Watkins
B E
BE
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
Esumi
H
H
Wakabayashi
K
K
Nagao
M
M
Sugimura
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D007093:Imidazoles / Q000493:pharmacokinetics*; D008297:Male; D009153:Mutagens / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine