Histone Adduction with Nicotine: A Bio-Ams Study

Abstract

Based on the study of DNA adduction with nicotine, we have measured the mouse hepatic histone adduction with 14C-labeled nicotine in vivo by bio-accelerator mass spectrometry (bio-AMS). In the exposure of mice to nicotine, the dose range administered was from 0.2 μg to 6.0 μg kg b.w.-1, which was equivalent to a very low level of human exposure to cigarette smoke. The adducts of either histone 1 (H1) or histone 3 (H3) with nicotine in mouse liver increased markedly with increasing nicotine dose. Our results have demonstrated that in the study of protein adduction with toxic xenobiotics as a biomarker, the AMS method achieves the highest sensitivity, 4.6 × 10-17 mol (46 amol) adducts per mg H1 protein, compared to all the other methods used previously.