Sjödin P, Wallin H, Alexander J, Jägerstad M
Department of Applied Nutrition, Chemical Center, Lund, Sweden.
Carcinogenesis. 1989 Jul;10(7):1269-75. doi: 10.1093/carcin/10.7.1269.
The disposition and metabolism of a common food mutagen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), was studied in rats. Five rats of both sexes were given a single oral dose of 14C-labeled MeIQx (3-4 mg/kg body wt). The male rats excreted 36% of the radioactivity and 15% of the mutagenic activity of the dose given in the urine collected during the first 24 h. In the females the corresponding urine contained 41% of the radioactivity and 12% of the mutagenicity. During the next 48 h only 1-3% of the radioactive dose was excreted in urine. The remaining dose was excreted in the feces except of less than 1% that was retained by the tissues after 72 h. The liver and kidney retained more radioactivity than other organs. In a separate study the metabolites of bile, urine and feces of both sexes were investigated. After a single oral dose of 20 mg 14C-labeled MeIQx/kg body wt, three major non-mutagenic metabolites were identified. These were 2-amino-4(or 5)-(beta-D-glucuronopyranosyloxy)-3,8-dimethylimidazo[4,5-f] quinoxaline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxalin-4(or 5)-yl sulfate and N-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl) sulfamate. Another two metabolites present in bile, urine and feces were 2-(beta-D-glucuronopyranosylamino)-3,8-dimethylimidazo[4,5-f ] quinoxaline and 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxalin-4 (or 5)yl sulfate. All metabolites were essentially non-mutagenic. Most of the mutagenicity still present in bile, urine and feces could be explained by unchanged MeIQx. Unchanged MeIQx was the most abundant form excreted in urine.
对常见食物诱变剂2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉（MeIQx）在大鼠体内的处置和代谢进行了研究。给5只雄性和5只雌性大鼠单次口服剂量为14C标记的MeIQx（3 - 4毫克/千克体重）。雄性大鼠在前24小时收集的尿液中排泄了给予剂量的36%放射性和15%诱变活性。雌性大鼠相应尿液中含有41%放射性和12%诱变活性。在接下来的48小时内，仅1 - 3%放射性剂量经尿液排泄。其余剂量经粪便排泄，72小时后组织留存不到1%。肝脏和肾脏留存的放射性比其他器官更多。在另一项研究中，对两性胆汁、尿液和粪便中的代谢物进行了研究。单次口服剂量为20毫克14C标记的MeIQx/千克体重后，鉴定出三种主要的非诱变代谢物。它们是2-氨基-4（或5）-（β-D-葡糖醛酸吡喃糖氧基）-3,8-二甲基咪唑并[4,5-f]喹喔啉、2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉-4（或5）-基硫酸盐和N-（3,8-二甲基咪唑并[4,5-f]喹喔啉-2-基）氨基磺酸酯。胆汁、尿液和粪便中存在的另外两种代谢物是2-（β-D-葡糖醛酸吡喃糖基氨基）-3,8-二甲基咪唑并[4,5-f]喹喔啉和2-氨基-8-羟甲基-3-甲基咪唑并[4,5-f]喹喔啉-4（或5）基硫酸盐。所有代谢物基本上都是非诱变的。胆汁、尿液和粪便中仍存在的大部分诱变活性可由未变化的MeIQx解释。未变化的MeIQx是尿液中排泄的最丰富形式。
