Department of Materials and Environmental Chemistry, Environmental Chemistry Unit, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
Chem Res Toxicol. 2011 Nov 21;24(11):1957-65. doi: 10.1021/tx200284u. Epub 2011 Sep 15.
The knowledge about fetal exposure to acrylamide/glycidamide from the maternal exposure through food is limited. Acrylamide, glycidamide, and ethylene oxide are electrophiles and form adducts with hemoglobin (Hb), which could be used for in vivo dose measurement. In this study, a method for analysis of Hb adducts by liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied to measurements of adducts from these compounds in maternal blood samples (n = 87) and umbilical cord blood samples (n = 219). The adduct levels from the three compounds, acrylamide, glycidamide, and ethylene oxide, were increased in tobacco smokers. Highly significant correlations were found between cord and maternal blood with regard to measured adduct levels of the three compounds. The mean cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27-0.86) for acrylamide, 0.38 (range 0.20-0.73) for glycidamide, and 0.43 (range 0.17-1.34) for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in maternal blood, which is compatible with the structural differences in fetal and adult Hb. Together, these results indicate a similar life span of fetal and maternal erythrocytes. The results showed that the in vivo dose in fetal and maternal blood is about the same and that the placenta gives negligible protection of the fetus to exposure from the investigated compounds. A trend of higher levels of the measured adducts in cord blood with gestational age was observed, which may reflect the gestational age-related change of the cord blood Hb composition toward a higher content of adult Hb. The results suggest that the Hb adduct levels measured in cord blood reflect the exposure to the fetus during the third trimester. The evaluation of the new analytical method showed that it is suitable for monitoring of background exposures of the investigated electrophilic compounds in large population studies.
关于母体通过食物暴露导致胎儿接触丙烯酰胺/环氧丙酰胺的知识有限。丙烯酰胺、环氧丙酰胺和环氧乙烷都是亲电试剂，与血红蛋白（Hb）形成加合物，可用于体内剂量测量。在这项研究中，应用液相色谱-质谱联用分析 Hb 加合物的方法，即 FIRE 程序，对来自母体血液样本（n=87）和脐带血样本（n=219）中这些化合物的加合物进行了测量。丙烯酰胺、环氧丙酰胺和环氧乙烷这三种化合物的加合物水平在吸烟母体中增加。在这三种化合物中，脐带血和母体血中的加合物水平之间存在高度显著的相关性。三种化合物的脐带/母体血红蛋白加合物水平比值的平均值分别为丙烯酰胺 0.48（范围 0.27-0.86）、环氧丙酰胺 0.38（范围 0.20-0.73）和环氧乙烷 0.43（范围 0.17-1.34）。丙烯酰胺和环氧丙酰胺的体外研究表明，与母体血中的 Hb 相比，脐带血中的 Hb 形成加合物的速度较低（0.38-0.48），这与胎儿和成人 Hb 的结构差异一致。总之，这些结果表明胎儿和母体红细胞的寿命相似。结果表明，胎儿和母体血液中的体内剂量大致相同，胎盘对胎儿对所研究化合物的暴露几乎没有保护作用。观察到脐带血中测量的加合物水平随胎龄呈上升趋势，这可能反映了脐带血 Hb 组成向成人 Hb 含量较高的胎龄相关变化。结果表明，脐带血中 Hb 加合物水平反映了胎儿在孕晚期的暴露情况。新分析方法的评估表明，该方法适用于监测大型人群研究中所研究亲电化合物的背景暴露情况。
