Weyand E H, Bevan D R
Cancer Res. 1986 Nov;46(11):5655-61.
[3H]Benzo(a)pyrene [B(a)P] disposition and metabolism were investigated in male Sprague-Dawley rats. [3H]B(a)P, in a vehicle of triethylene glycol, was administered by intratracheal instillation (1 microgram/kg body weight), and the amount of radioactivity in various organs was determined at timed intervals between 5 and 360 min. Elimination of radioactivity from lungs was biphasic with half-lives of 5 and 116 min. Radioactivity in liver increased rapidly, reaching a maximum of 21% of the dose within 10 min after instillation and decreasing thereafter until less than 5% of the dose was detected at 360 min after instillation. The carcass accounted for 15-30% of the dose within the time intervals investigated. Toxicokinetic parameters to describe elimination of unmetabolized B(a)P from blood following intratracheal administration were found to be very similar to those calculated following i.v. administration. B(a)P metabolites in lung, liver, and intestinal contents were identified. Notably, quinones were at highest concentrations in both lung and liver 5 min after instillation, accounting for 12 and 7% of organic extractable material, respectively. B(a)P disposition was also investigated in animals with and without biliary cannulas. Distribution patterns among organs were similar though the amount excreted in bile and intestinal contents was 74 and 40% of the dose, respectively. Types of metabolites in bile and intestinal contents were identified and compared. Lower fractions of the administered dose were detected as thioether and glucuronic acid conjugates in intestinal contents than in bile, indicating that enterohepatic circulation of B(a)P metabolites was occurring.
研究了雄性斯普拉格-道利大鼠体内[³H]苯并(a)芘[B(a)P]的处置和代谢情况。[³H]B(a)P以三甘醇为载体，通过气管内滴注给药（1微克/千克体重），并在5至360分钟的时间间隔内定时测定各器官中的放射性活度。肺部放射性的消除呈双相性，半衰期分别为5分钟和116分钟。肝脏中的放射性迅速增加，在滴注后10分钟内达到剂量的21%的最大值，此后逐渐下降，直到滴注后360分钟检测到的剂量低于5%。在所研究的时间间隔内， carcass占剂量的15 - 30%。发现描述气管内给药后血液中未代谢B(a)P消除的毒代动力学参数与静脉内给药后计算的参数非常相似。鉴定了肺、肝和肠道内容物中的B(a)P代谢物。值得注意的是，滴注后5分钟，醌在肺和肝中的浓度最高，分别占有机可提取物的12%和7%。还研究了有和没有胆管插管的动物体内B(a)P的处置情况。尽管胆汁和肠道内容物中的排泄量分别为剂量的74%和40%，但各器官之间的分布模式相似。鉴定并比较了胆汁和肠道内容物中代谢物的类型。与胆汁相比，肠道内容物中作为硫醚和葡萄糖醛酸结合物检测到的给药剂量比例较低，这表明B(a)P代谢物的肝肠循环正在发生。
