GENOTOXICITY STUDY ON NICOTINE AND NICOTINE-DERIVED NITROSAMINE BY ACCELERATOR MASS-SPECTROMETRY

We have studied DNA adduction with C-14-labeled nicotine and nicotine- derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (N NK), by accelerator mass spectrometry (AMS) in mouse liver at doses eq uivalent to low-level exposure of humans. The dose ranges of nicotine and NNK administered were from 0.4 mu g to 4.0 x 10(2) mu g kg b.w.(-1 ), and from 0.1 mu g to 2.0 x 10(4) mu g kg b.w.(-1), respectively. In the exposure of mice to either nicotine or NNK, the number of DNA add ucts increased linearly with increasing dose. The detection limit of D NA adducts was 1 adduct per 10(11) nucleotide molecules. This limit is 1-4 orders of magnitude lower than that of other techniques used for quantification of DNA adducts. The results of our animal experiments e nabled us to speculate that nicotine is a potential carcinogen. Accord ing to the procedure for C-14-labeled-NNK synthesis, we discuss the ul timate chemical speciation of NNK bound to DNA. From the animal tests we derived a directly perceivable relation between tobacco consumption and DNA adduction as the carcinogenic risk assessment.