Interaction of tobacco chewing and smoking habit with interleukin 6 promoter polymorphism in oral precancerous lesions and oral cancer.

OBJECTIVE: Our study aims to determine the influence of smoking or tobacco chewing and the association of Interleukin 6 (IL-6) polymorphism, where G is substituted by A at the position - 596 (IL-6 - 596 G/A) and substitution of G by cytosine (C) at position - 572 (IL-6 - 572 G/C) on the susceptibility of precancerous oral lesions and oral cancer. MATERIALS AND METHODS: The participants consisted of 250 subjects among which 75 were suffering from oral cancer, 75 subjects with precancerous oral lesions and 100 were healthy controls. Single-nucleotide polymorphism study (SNP) was done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: IL-6 - 596 G/A SNP revealed genotypes, GG, and GA in subjects with precancerous oral lesions and oral cancer, and AA genotype was not found in any subject. IL-6 - 596 G/A was strongly associated with oral precancerous lesions but not with oral cancer. The present study reports that smokers carrying GA for IL-6 - 596 G/A were at several folds higher risk of developing oral precancerous lesions. Smokers with GC and CC for IL-6 - 572 G/C were at higher risk of developing oral precancerous lesions. No significant interaction was observed between these habits and IL-6 - 596 G/A and IL-6 - 572 G/C SNP with oral cancer. CONCLUSION: The interaction of variant A allele of IL-6 - 596 G/A and C allele of IL-6 - 572 G/C polymorphism with smoking and increases the risk of oral precancerous lesions. Tobacco chewing was not related with IL-6 - 596 G/A or IL-6 - 572 G/C in oral precancerous lesions or oral cancer. CLINICAL RELEVANCE: The study will help to determine the susceptibility of individuals with smoking or chewing habits to the development of oral precancerous lesion and oral cancer by monitoring the IL-6 SNPs which can be used as a biomarker for risk determination.

ROS-dependent Bax/Bcl2 and caspase 3 pathway-mediated apoptosis induced by zineb in human keratinocyte cells.

There are a large number of agricultural workers who are exposed to pesticides through skin and inhalation. The best approach to identify altered molecular pathways during dermal exposure to pesticides is relevant to risk-associated concern about skin safety. In this study, we investigated the cytotoxic effect of zineb, a fungicide, in human keratinocyte (HaCaT) cells. HaCaT cells were treated with zineb (1-40 µg/mL) for 24 hours. Cellular and molecular mechanisms of cell toxicity were investigated through MTT and neutral red-uptake assays. Zineb reduced viability of HaCaT cells and induced apoptosis in a concentration-dependent manner. Zineb increased levels of Bax and caspase 3 and inhibited the level of Bcl2, which subsequently induced apoptosis via the Bax/Bcl2 and caspase pathway. Therefore, zineb could have induced apoptosis through the mitochondrial pathway in HaCaT cells. Our study suggests that zineb is cytotoxic to HaCaT cells via the induction of apoptosis and oxidative stress in vitro.