Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

Abstract

International Journal of Occupational Medicine and Environmental AbstractDecember 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden and accidental leakage of deadly poisonous methyl isocyanate (MIC) gas instigated research efforts to understand the nature, severity of health damage and sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period, our systematic laboratory investigations coupled with long-term molecular surveillance studies have comprehensively demonstrated that the risk of developing an environmental associated aberrant disease phenotype, including cancer, involves complex interplay of genomic and epigenetic reprogramming. These findings poised us to translate this knowledge into an investigative framework of "molecu lar biodosimetry" in a strictly selected cohort of MIC exposed individuals. A pragmatic cancer risk-assessment strategy pursued in concert with a large-scale epidemiological study might unfold molecular underpinnings of host-susceptibility and exposureresponse relationship. The challenges are enormous, but we postulate that the study will be necessary to establish a direct initiation-promotion paradigm of environmental carcinogenesis. Given that mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently linked to neoplasticity, a cutting-edge tailored approach by an expert pool of biomedical researchers will be fundamental to drive these strategies from planning to execution. Validating the epigenomic signatures will hopefully result in the development of biomarkers to better protect human lives in an overburdened ecosystem, such as India, which is continuously challenged to meet population demands. Besides, delineating the mechanistic links between MIC exposure and cancer morbidity, our investigative strategy might help to formulate suitable regulatory policies and measures to reduce the overall burden of occupational and environmental carcinogenesis.

Fetal nucleic acids in maternal plasma from biology to clinical translation

“…human tragedies demonstrated the sensitivity of the developmental period to environmental exposures (9)(10)(11)(12). The contamination of mercury resulted in severe brain dysfunction in children due to high mercury exposure of pregnant women in Minamata Bay of Japan (13); PCB contamination of rice oil in Japan where exposed mothers have lower IQ children as compared to the unexposed ones (14); the Seveso explosion had trans-generational effect in the offspring of the mothers exposed to high concentrations of dioxin during pregnancy at a manufacturing plant near Italy (15); in utero MIC exposure during the Bhopal gas tragedy which caused a persistently hyper-responsive cellular and humoral immune state in affected individuals with increased cytokine secretions, higher immunoglobulin levels and anti-nuclear antibodies (16)(17)(18).…”

Effects of carbamate pesticides intermediates on Escherichia coli membrane architecture: An in vitro and in silico approach

“…Methyl isocyanate is utilized as an intermediate in the production of carbamate pesticides which were accidentally released from the Union Carbide India Limited (UCIL) plant in the Bhopal gas tragedy, the world's most horrible industrial disaster [6][7][8]. Thousands of people died with pulmonary oedema, and thousand survived with various diseases like cancer, pulmonary, reproductive, ophthalmic, hematologic, tuberculosis, immunologic and neurological toxicity [9][10][11]. Numerous theories have suggested for the interaction of MIC with different cell lines MM55.K, B/CCMA.OV, NIH.3T3 and cultured human lymphocytes which justify its toxicological effect [12].…”

Use and limitations of offsite consequence analysis tools from South Korea and the United States in hydrogen fluoride accidental release

“…Chemicals are used in various forms in our everyday lives and in industry, and they can be causes of big and small accidents (Lee et al ). Some chemical leakage accidents worldwide include a dioxin leak in Seveso, Italy, in 1976 (Orford et al ), a toxic gas leak from a Bhopal pesticide plant in India in 1984 (Mishra et al ), and a hydrofluoric acid (HF) leak from the Foshan oil refinery company in the United States (US) in 1987 (Wing et al ; Kim et al ). In 2012, an HF leak accident in Gumi, South Korea, caused 5 deaths, injuries to 18 people, health problems, and crop damage in nearby areas (Lee ).…”