ToxSci Advance Access originally published online on April 27, 2005
Toxicological Sciences 2005 86(2):309-317; doi:10.1093/toxsci/kfi186
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The Tobacco Alkaloid Nicotine Demonstrates Genotoxicity in Human Tonsillar Tissue and Lymphocytes
* Department of Otolaryngology–Head and Neck Surgery, University of Regensburg, D-93053 Regensburg, Germany; Department of Otolaryngology–Head and Neck Surgery, Ludwig-Maximilians University Munich, D-80337 Munich, Germany; Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians University Munich, D-80337 Munich, Germany
Received January 27, 2005; accepted April 25, 2005
Recent studies suggest a direct contribution of nicotine, the addictive component of tobacco and tobacco smoke, to human carcinogenesis. To assess the genotoxicity of nicotine, the DNA-damaging effect on human lymphocytes and target cells from lymphatic tissue of the palatine tonsils from 10 healthy patients was tested with the alkaline single-cell microgel electrophoresis (Comet) assay. The degree of DNA migration, a measure of possible DNA single strand breaks, alkali labile sites, and incomplete excision repair sites, was expressed as the Olive tail moment, the percentage of DNA in the tail, and the tail length. One hour exposure to nicotine at 0.125, 0.25, 0.5, 1, 2, and 4 mM induced a statistically significant dose-dependent increase of DNA migration up to 3.8-fold and 3.2-fold in tonsillar cells and lymphocytes, respectively. The lowest concentration eliciting significant DNA damage was 0.5 mM nicotine. The genotoxic effect was confirmed in a second series of experiments using nicotine of high purity from two different suppliers. There were no significant differences between the two series, excluding artifacts from the source of nicotine. Finally, DNA damage by nicotine was compared in cells incubated in medium strictly adjusted to neutral pH, with nonadjusted medium becoming alkaline with increasing nicotine concentrations. Again no differences in DNA migration were observed. The data indicate that nicotine expresses significant direct genotoxic effects in human target cells in vitro. However, no differences in DNA damage were observed in cells from smokers and nonsmokers incubated without nicotine. The lack of higher DNA damage in smokers compared to nonsmokers could be a question of nicotine dose, rapid DNA repair, or interactions with other smoke constituents. These results require further investigations on the contribution of nicotine to tobacco carcinogenesis.
Key Words: genotoxicity; nicotine; Comet assay; human target cells.
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