European Journal of Cardiovascular Medicine

Aims and objective: Apoptosis is essential physiological process of eliminating cells with damaged DNA. Any alterations in the apoptotic pathway may result increased malignant potential. Oral leukoplakia is an important health issue, especially in countries where the use of tobacco is almost a social habit. A significant proportion of cases of oral leukoplakia progress to the squamous cell carcinoma. Although the role of tobacco in causation and malignant transformation of oral leukoplakia is well established, but the cellular pathways affected by the tobacco use are not yet clear. The aim of the present paper was to study the effect of tobacco in alteration of apoptosis and proteins involved in apoptotic pathway and K-ras in oral leukoplakia. Material and Methods: Two hundred and thirty cases of oral leukoplakia were included in the study. These cases were divided into tobacco-consuming and non tobacco-consuming groups depending upon the history of tobacco intake (smoking or chewing). The presence and grade of dysplasia was noted from the histopathological reports. The apoptotic cells were identified by in-situ terminal TdT-mediated dUTP-biotin nick-end labeling (TUNEL). The expression of caspase-3, caspase-8, caspase-9, bax and K-ras was studied in all the cases by immunohistochemistry. The apoptosis and caspase protein expression was then compared with control subjects using chi-square test. Result: The cases diagnosed with leukoplakia were grouped according to use of tobacco. In both the groups a statistical significant increase in apoptosis, caspase-3, caspase-8, caspase-9, bax and K-ras was observed as compared to controls.  On comparison between the groups, the apoptosis and proteins involved in apoptotic pathway in tobacco group with dysplasia were significantly lower than the non tobacco-consuming group with dysplasia. An increase in K-ras oncogene expression was found in leukoplakia-dysplasia of tobacco-consuming group. Conclusion: A significant decrease in the proteins mediating the extrinsic and intrinsic pathway of apoptosis was observed in the tobacco-consuming group, which indicates possible role of tobacco carcinogens in malignant transformation of oral leukoplakia.