关键词: 生物加速器质谱法, 尼古丁, 组蛋白, 加合, 生物标志物

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