Abstract: Since 1992 we have carried out the accelerator mass spectrometry(AMS) study of the bio-macromolecule adduction in vivo with the tobacco specific ¹⁴C labeled nicotine and its nitrosamine derivative NNK. We quantified the DNA adducts as well as the histones (H1 and H3) adducts in mouse liver by means of the AMS system on the 2×6 MV EN Tandem of the Institute of Heavy Ion Physics, Peking University. In most cases, the dose range administered was from 0.1 to 400 microgram/kg b.w., the lower levels of which were equivalent to the human exposure to the environmental cigarette smoke. In all the adduction systems studied the definite biomacromolecule adduction with nicotine or NNK was observed. The number of adducts increased with increasing dose in different graphic fashions, exponential, linear or non-linear. The DNA adduction is well recognized as an effective biomarker or molecular dosimeter, indicating the early detectable and critical step of chemical mutagenesis and carcinogenesis. Our findings have revealed the fact that nicotine per se is a potential carcinogen other than the well-known addiction fact. Besides, we first observed the histones adduction with nicotine that did harm to the gene-regulatory function of the DNA binding protein histones. The detection limit of adducts was 1 adduct per 10¹⁰ nucleotides for DNA and 4.6×10^-17mol/mg H1 protein for histone. The latter is the highest sensitivity to date in biomarker measurements compared to the data previously reported.

Key words: bio-accelerator mass spectrometry, nicotine, histones, adduction, biomarker

摘要： 自1992年以来，使用北京大学重离子物理研究所的2×6 MV EN型串列静电加速器上的加速器质谱仪(AMS)，较系统地研究了¹⁴C标记的尼古丁和鼠肝、肺细胞核DNA的加合，以及和鼠肝细胞核组蛋白的加合。在这些体内生物大分子中均观察到肯定的加合作用。加合物数目随尼古丁的动物剂量的增加而增加，剂量响应呈指数直线关系或非指数直线或曲线关系。实验结果表明尼古丁不仅是公认的吸烟上瘾的主要因子，而且可能是致癌物质。AMS测量灵敏度达很高水平：每10¹⁰个核苷酸可检测的最低限量为1个加合物和每mg(毫克)H1蛋白质可检测的最低限量为4.6×10^-17mol加合物，后者高于前人报道过的灵敏度。生物加速器质谱法可以为基因毒性研究提供极灵敏的生物标志物。

关键词: 生物加速器质谱法, 尼古丁, 组蛋白, 加合, 生物标志物