Albrecht O E, Filser J G, Neumann H G
Institute of Toxicology, University of Würzburg, Germany.
IARC Sci Publ. 1993(127):135-42.
The adduct formed by the reaction of 1,3-butadiene monoxide, a major metabolite of the mutagen and carcinogen 1,3-butadiene, with the N-terminal valine of haemoglobin was used as a dosimeter for the bioavailability of reactive metabolites. The dose-dependence of adduct formation was studied in female CB6F1 mice and female Wistar rats exposed to 0, 50, 200, 500 or 1300 ppm butadiene in an open inhalation chamber for 6 h per day for five consecutive days. Globin was isolated 18 h after the last exposure, and N-terminal valine was obtained by a modified Edman degradation procedure. Adduct levels were five times higher in mice than in rats (17 and 3.5 nmol/g globin, respectively, at 500 ppm), which may partially explain the greater susceptibility of mice to tumour formation. Adduct levels increased linearly with dose in rats, whereas in mice this slope of the curve became flatter at 500 ppm and increased with higher doses. Similar results were obtained in male and female C3H x 101/EL mice.
1,3 - 丁二烯（一种诱变剂和致癌物）的主要代谢产物1,3 - 丁二烯 monoxide与血红蛋白的N - 末端缬氨酸反应形成的加合物，被用作反应性代谢产物生物利用度的剂量计。在开放吸入室中，对雌性CB6F1小鼠和雌性Wistar大鼠连续五天每天暴露于0、50、200、500或1300 ppm丁二烯6小时，研究加合物形成的剂量依赖性。在最后一次暴露18小时后分离珠蛋白，并通过改良的埃德曼降解程序获得N - 末端缬氨酸。小鼠中的加合物水平比大鼠高五倍（在500 ppm时分别为17和3.5 nmol/g珠蛋白），这可能部分解释了小鼠对肿瘤形成的易感性更高。大鼠中的加合物水平随剂量呈线性增加，而在小鼠中，曲线斜率在500 ppm时变得更平缓，并随着更高剂量而增加。在雄性和雌性C3H x 101/EL小鼠中也获得了类似结果。
