Sepai O, Anderson D, Street B, Bird I, Farmer P B, Bailey E
MRC Toxicology Unit, Carshalton, Surrey, UK.
Arch Toxicol. 1993;67(1):28-33. doi: 10.1007/BF02072031.
Styrene oxide, which is the genotoxically active metabolite of styrene, reacts in vivo with carboxylic acid residues in hemoglobin forming phenylhydroxyethyl esters. Mild alkali hydrolysis cleaves these ester adducts, yielding styrene glycol, which in human blood labelled in vitro with 14C-styrene oxide accounted for 15% of the total radioactivity covalently bound to the protein. A quantitative assay procedure has been developed for measuring the base released styrene glycol in globin. The method utilizes solvent extraction followed by trimethylsilyl ether derivatization and separation and quantitation by capillary gas chromatography with selective ion recording mass spectrometry. Globin labelled in vitro with d8-styrene oxide was used as the internal standard. The method was used to establish a dose-response relationship in rats given single i.p. doses of styrene oxide (83.3-833 mumol/kg body wt). The method, which allows quantitation of the adducts down to levels of 15 pmol/g globin, has the potential to act as a dosimeter for industrial workers exposed to styrene or styrene oxide.
氧化苯乙烯是苯乙烯具有遗传毒性的活性代谢产物，在体内它与血红蛋白中的羧酸残基发生反应，形成苯羟乙基酯。温和的碱水解作用会裂解这些酯加合物，生成苯乙二醇，在体外用(^{14}C -)氧化苯乙烯标记的人血中，苯乙二醇占与蛋白质共价结合的总放射性的(15%)。已开发出一种定量测定方法，用于测量球蛋白中碱释放的苯乙二醇。该方法采用溶剂萃取，然后进行三甲基硅醚衍生化，再通过带有选择性离子记录质谱的毛细管气相色谱进行分离和定量。体外用(d8 -)氧化苯乙烯标记的球蛋白用作内标。该方法用于建立经腹腔单次注射氧化苯乙烯（(83.3 - 833)微摩尔/千克体重）的大鼠的剂量 - 反应关系。该方法能够定量低至(15)皮摩尔/克球蛋白水平的加合物，有可能作为接触苯乙烯或氧化苯乙烯的产业工人的剂量计。
