加速器质谱法研究尼古丁与小鼠血液蛋白的加合作用

Accelerator Mass Spectrometry Studies on Adduction of Nicotine with Hemoglobin and Serum Albumin in Mouse

采用加速器质谱法（AMS）研究了小鼠血液中的血红蛋白（Hb）、白蛋白（SA）和尼古丁的加合作用．在尼古丁剂量从相应于人吸烟的环境剂量水平0．1μg／kg体重到 100 μg／kg体重范围内，测量了尼古丁－血红蛋白加合物和尼古丁－白蛋白加合物的剂量效应曲线．两种蛋白的尼古丁加合物水平都随着尼古丁剂量的升高而线性增加．在实验剂量范围内，两种蛋白质加合物的水平与小鼠肝DNA加合物水平也呈现良好的线性关系．这说明两种蛋白质加合物均可以替代DNA加合物作为尼古丁的生物标记物．在本工作中，蛋白质加合物的测量灵敏度为 0．03 pmol／g 蛋白（即 3．2个加合物/ 1012氨基酸残基），达到了文献报道的测量蛋白质生物标记物最高的灵敏度．

Abstract Adducts of hemoglobin(Hb) and serum albumin(SA) with nicotine in mouse blood were mea-sured respectively by using accelerator mass spectrometry (AMS). The dose response of adduct levels ofHb/SA and the correlative relationship between the two blood protein adducts were investigated over arange of doses(0. 1-100. 0 μg/kg body weight), which were equivalent to a low-level dose of environ-mental exposure of cigarette smoking. Both the levels of Hb and SA adducts increased with increasing doseand showed a linear relationship. By plotting Hb/SA adducts versus DNA adducts, a linear relationship fitsthe experimental observations best, which means that Hb/SA adduct could substitute for DNA adduct as abiomarker for nicotine. The detection limit of protein adduct in this work is 0. 03 pmol/g protein(namely3. 2 adducts/1012 amino acid residues), the excellent sensitivity in protein biomarker measurements com-pared to the data reported previously.