Fate and distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats.
Fate and distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats.
复制标题
2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）在大鼠体内的命运和分布。
作者：
B. Watkins;H. Esumi;K. Wakabayashi;M. Nagao;T. Sugimura
Fischer 344 只大鼠通过灌胃给予单剂量 0.60 mg/只的 [2-14C]2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶 (PhIP)；给药后12、24、48、96小时测定粪便、尿液、血液、血清蛋白、血红蛋白和组织中的放射性。在尿液中发现了一种主要和四种次要的含放射性成分，在粪便中发现了一种主要和两种次要的含放射性成分。粪便是主要排泄途径，在前24小时内占剂量的78%，粪便中未变化的PhIP占剂量的51%。未代谢的 PhIP 也被证明是腹腔注射单剂量动物胆汁和粪便中的主要放射性成分。注射。血液中含有一小部分剂量，血液中主要的、持久结合的 PhIP 形式是与血红蛋白结合。给药后 12 小时，结肠和盲肠含有最高浓度的放射性，而稍后时间肾脏和肝脏显示出最高浓度。在 24 小时后的时间点，组织中含有的放射性 80-90% 不溶于乙醇，表明它与大分子共价结合。
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.