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ToxSci Advance Access published online on January 12, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh061
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received October 17, 2003; accepted December 12, 2003
© 2004 Society of Toxicology

Genetic Toxicology

Genotoxic and Antiapoptotic Effect of Nicotine on Human Gingival Fibroblasts

Gabriella Argentin 1* and Rosadele Cicchetti 1

1 Department of Public Health and Cellular Biology, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy

* To whom correspondence should be addressed. E-mail: argentin{at}med.uniroma2.it.


  Abstract

Growing evidence suggests that nicotine, the addictive component of cigarette smoke, can have a direct role in tumour development, enhancing cell proliferation and impairing apoptotic process in certain types of human cancer cell lines. Since the correlation between apoptosis and DNA damage is already well documented, we investigated the response of human gingival fibroblasts (HFGs) to nicotine-exposure by examining its effect on DNA damage induction and apoptotic process in parallel. To assess the genotoxicity of this drug, the cytokinesis-block micronucleus (CBMN) test was performed. Treatment of HGFs with nicotine at a concentration (1[mu]M) causes a statistically significant increase of micronucleus (MN) frequency at the tested time intervals, while no change was detected in cell growth under the same conditions. Furthermore, we here report that pre-incubation of HGFs with 1[mu]M nicotine strongly attenuates staurosporine (STP)- induced apoptosis. Finally, we demonstrate that cultures exposed to nicotine show an increase of reactive oxygen species, as determined by increased levels of 2,7 dichlorofluorescein (DCF). When cells were pre-labelled with N-acetyl-cysteine (NAC), a substrate for glutathione synthesis, and catalase (CAT), oxygen free radical scavenger, a significant reduction in cytogenetic damage was observed.

Thus, for the first time a concomitant genotoxic and antiapoptotic effect of nicotine was reported in HGFs.


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