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The complicated pathogenic impacts of CS are considered as the attribution that leads to OLK and even its malignant transformation, In a prior study by Ye et al., they found that the immortalized human oral mucosa epithelial cell line leuk1 could significantly accumulated reactive oxygen species (ROS) upon cigarette smoke extract (CSE) exposure compared to the unexposed co-cultured cells, indicating the destructive effect of oxidative stress on the structure and function of oral epithelium [27]