A Retrospective and Prospective Analysis of Molecular Signature Patterns and Genomic Instability Profiles Among First and Second Generation Victims of Bhopal Gas Tragedy Diagnosed With Gastrointestinal Malignancies

Abstract

Although it has been known since the early 1900s that accidental or occupational exposure to newlinecertain environmentally hazardous chemicals can induce severe health effects, industrial newlinechemical disasters such as that of Bhopal Gas Tragedy and other disasters of both national newlineand international prominence have renewed interest in this discipline. The disaster indicated newlinea need for enforceable international standards for the environmental protection, preventative newlineapproaches to avoid similar accidents and industrial disaster awareness. Chemicals can cause newlinehigh mortality, slow down growth or disturb various body systems. Isocyanates, including newlineMIC despite their wide industrial applications are known to exert mutagenic and genomic newlinealterations (Anderson et al., 1988; Mishra et al., 2008). Therefore, genomic integrity of cells newlineis often challenged by both chemical and physical agents that can modify the bases of newlinenucleotides and modify or break the sugar-phosphate backbone. When a human cell detects newlinedamaged DNA, it initiates the DNA damage response (DDR) that permits it to repair the newlinedamage and avoid transmitting it to daughter cells. Despite this comeback of cellular repair newlinemachinery, changes to the genome arise and some cells, such as proliferating cancer cells, are newlineprone to genome instability (Swift and Golsteyn, 2014). newlineThe process of gallbladder carcinogenesis is usually related to a history of gallstone disease, newlinewhich is frequently present for at least 20 years before the tumor appears. However, multiple newlinerisk factors exist, including endogenous and exogenous like genetic factors and gene newlinemutations and sun exposure, chemical carcinogens and other environmental stress (Gordon, newline2013). Early diagnosis and treatment are needed to decrease the number of deaths due to newlinegallbladder cancer. Whereas, the precise molecular mechanism of gallbladder cancer remains newlineunclear, which make it difficult for treatment of the disease. T