Nicotinic receptors mediate tumorigenic action of tobacco-derived nitrosamines on immortalized oral epithelial cells (original) (raw)

Inhibition of nitric oxide-induced apoptosis by nicotine in oral epithelial cells

Molecular and Cellular Biochemistry, 2007

Development of oral cancer is clearly linked to the usage of smokeless tobacco. The molecular mechanisms involved in this process are however not well understood. Toward this goal, we investigated the effect of smokeless tobacco exposure on apoptosis of oral epithelial cells. Exposure of oral epithelial cells to smokeless tobacco extract (STE) induces apoptosis in a dose-dependent manner, until a threshold level of nicotine is achieved upon which apoptosis is inhibited. 1 mM of nicotine is able to inhibit apoptosis significantly induced by STE in these oral cells. Exposure of cells to nicotine alone has no effect on apoptosis, but nicotine inhibits apoptosis induced by other agents present in STE. In this study we show that, the antiapoptotic action of nicotine is specifically associated with down-regulation of nitric oxide (NO) production. Using specific inducers of NO, we have demonstrated that inhibition of apoptosis by nicotine is through down-regulation of NO production. Further, we observed that nicotine clearly acts as a sink of NO radicals, shown using peroxynitrite generator (SIN-1) in conjunction or absence of radical scavengers. Nicotine thus causes most damage in transformed epithelial cells as depicted by accumulation of nitrotyrosine in a 3-NT ELISA assay. Inhibition of apoptosis is a hallmark in tumor progression and propels development of cancer. It may further result in functional loss of apoptotic effector mechanisms in the transformed cells. Thus, our data clearly indicates that inhibition of NOinduced apoptosis by nicotine may lead to tobacco-induced oral carcinogenesis, and implies careful development of modalities in tobacco cessation programs. Keywords Nicotine Á Apoptosis Á Nitric oxide Á Inhibition Á Oral epithelial cells Á HCPC-1 Á Fibroblasts Á RPDL Á Reactive oxygen species Á Peroxynitrite radical Á Nitrotyrosination Á 3-NT Abhijit G. Banerjee and Velliyur K. Gopalakrishnan-contributed equally.

Tobacco-specific nitrosamines: A literature review

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2018

Cigarette smoke is a complex mixture of chemicals, including several tobacco-specific nitrosamines (TSNA). Most TSNA are formed in tobacco during the post-harvest period, while a number are produced when a cigarette is burned. Considerable evidence supports the role of TSNA important causative factors for cancers of the lung, pancreas, esophagus, and oral cavity in people who use tobacco products. Of the known TSNA, nicotine-derived nitrosamine ketone (NNK) and N-nitrosonornicotine (NNN) are the most carcinogenic. Other TSNA include N'-nitrosoanatabine (NAT) and N-nitrosoanabasine (NAB). New tobacco products (e.g., e-cigarettes) designed to attract consumers who are concerned about the health effects of tobacco have been appearing on the market. Several studies have reported that certain TSNA have been detected in the replacement liquids and vapour of e-cigarettes, but the levels are generally considerably lower than in tobacco cigarettes. Additionally, the FDA recently announce...