X. S. Li, H. F. Wang, J. Y. Shi, X. Y. Wang, Y. F. Liu, K. Li, X. Y. Lu, J. J. Wang, K. X. Liu and Z. Y. Guo
We have studied DNA adduction with 14C-labeled nicotine and nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK), by accelerator mass spectrometry (AMS) in mouse liver at doses equivalent to low-level exposure of humans. The dose ranges of nicotine and NNK administered were from 0.4 µg to 4.0 x 10^2 µg kg b.w.-1, and from 0.1 µg to 2.0 x 10^4 µg kg b.w.-1, respectively. In the exposure of mice to either nicotine or NNK, the number of DNA adducts increased linearly with increasing dose. The detection limit of DNA 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 enabled us to speculate that nicotine is a potential carcinogen. According to the procedure for 14C-labeled-NNK synthesis, we discuss the ultimate 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.
[Radiocarbon Volume 38, Number 2, 1996]