Methyl isocyanate may have a role in cancer etiology, although the link is unclear. There is evidence in the literature that it can induce cancer in animals but the carcinogenic potency is weak. Pheochromocytoma of adrenal medulla and acinar cell tumors of pancreas have been observed in methyl isocyanate exposed animals. Conversely, emerging data from population-based epidemiological studies are contradictory since there is no evidence of such cancers in methyl isocyanate exposed humans. Recently, we reported a high prevalence of breast and lung cancers in such a population in Bhopal. In vitro findings appearing in the latest scientific literature suggest that genomic instability is caused by methyl isocyanate analogs in lung, colon, kidney, ovary epithelial cells, and that hepatocytes may undergo oncogenic transformation, have obvious implications. The conflicting information prompted us to present this update over the last three decades on methyl isocyanate-induced cancers after an extensive literature search using PubMed. While the pertinent literature remains limited, with a scarcity of strong laboratory analyses and field-epidemiological investigations, our succinct review of animal and human epidemiological data including in vitro evidences, should hopefully provide more insight to researchers, toxicologists, and public health professionals concerned with validation of the carcinogenicity of methyl isocyanate in humans.

The Bhopal gas tragedy involving methyl isocyanate (MIC) is one of the most horrific industrial accidents in recent decades. We investigated the genotoxic effects of MIC in long-term survivors and their offspring born after the 1984 occurrence. There are a few cytogenetic reports showing genetic damage in the MIC-exposed survivors, but there is no information about the associated cancer risk. The same is true about offspring. For the first time, we here assessed the micronucleus (MN) frequency using cytokinesis-blocked micronucleus (CBMN) assay to predict cancer risk in the MIC-affected population of Bhopal. A total of 92 healthy volunteers (46 MICaffected and 46 controls) from Bhopal and various regions of India were studied taking gender and age into consideration. Binucleated lymphocytes with micronuclei (BNMN), total number of micronuclei in lymphocytes (MNL), and nuclear division index (NDI) frequencies and their relationship to age, gender and several lifestyle variabilities (smoking, alcohol consumption and tobacco-chewing) were investigated. Our observations showed relatively higher BNMN and MNL (P<0.05) in the MIC-affected than in the controls. Exposed females (EF) exhibited significantly higher BNMN and MNL (P<0.01) than their unexposed counterparts. Similarly, female offspring of the exposed (FOE) also suffered higher BNMN and MNL (P<0.05) than in controls. A significant reduction in NDI (P<0.05) was found only in EF. The affected group of non-smokers and non-alcoholics featured a higher frequency of BNMN and MNL than the control group of non-smokers and non-alcoholics (P<0.01). Similarly, the affected group of tobacco chewers showed significantly higher BNMN and MNL (P<0.001) than the non-chewers. Amongst the affected, smoking and alcohol consumption were not associated with statistically significant differences in BNMN, MNL and NDI. Nevertheless, tobacco-chewing had a preponderant effect with respect to MNL. A reasonable correlation between MNL and lifestyle habits (smoking, alcohol consumption and tobacco-chewing) was observed only in the controls. Our results suggest that EF and FOE are more susceptible to cancer development, as compared to EM and MOE. The genotoxic outcome detected in FOE reflects their parental exposure to MIC. Briefly, the observed cytogenetic damage to the MIC-affected could contribute to cancer risk, especially in the EF and FOE.

Methyl isocyanate (MIC) is a toxic industrial chemical that is documented as a potent respiratory toxicant. We investigated cell-mediated immunity (CMI) in the MIC-exposed long-term survivors and their offspring born after the Bhopal gas-leak tragedy in 1984. Several earlier reports show inconsistency in the assessment of immunological effects of MIC on the human population. In these studies, important factors including lifestyle attributes were overlooked. We incorporated these factors also in our study of the basic cell-mediated immune function in the Bhopal MIC-affected population. Twenty-seven years after exposure, we assessed the circulating T-lymphocyte frequency using E-Rosette assay. A total of 46 MIC-exposed healthy long-term survivors and their offspring were studied vis-a-vis parallel gender-age group-matched unexposed controls from Bhopal and various other regions of India. The influence of several lifestyle variabilities (smoking, alcohol intake, and tobacco chewing) on T-lymphocyte frequency was also taken into consideration. Our observations suggest that Erythrocyte-Rosette-forming cell (E-RFC) distribution frequency is largely insignificant in the MIC-affected population as compared to controls ( p > 0.05). In the MIC-affected tobacco chewers, there was a trend of suppression in CMI (relative decrease = 10.3%) as compared to nonchewers. Overall, our results show negligible long-term effect of MIC on CMI measured in terms of E-RFC frequency. These observations are not in agreement with earlier findings that immunosuppressive effects of MIC exposure persist in the T-cells of the affected population. However, atypical lymphocytes were frequently observed as E-RFC in the exposed females when compared to all other subgroups. Hematopoietic disorders (atypical lymphocytosis) in the MIC-affected population along with previous reports on the cytogenetic and humoral immune system linking cancer risk and chronic obstructive pulmonary disease (COPD) are important.

DNA methyltransferase 1 (DNMT1) is a relatively large protein family responsible for maintenance of normal methylation, cell growth and survival in mammals. Toxic industrial chemical exposure associated methylation misregulation has been shown to have epigenetic influence. Such misregulation could effectively contribute to cancer development and progression. Methyl isocyanate (MIC) is a noxious industrial chemical used extensively in the production of carbamate pesticides. We here applied an in silico molecular docking approach to study the interaction of MIC with diverse domains of DNMT1, to predict cancer risk in the Bhopal population exposed to MIC during 1984. For the first time, we investigated the interaction of MIC and its hydrolytic product (1,3-dimethylurea) with DNMT1 interacting (such as DMAP1, RFTS, and CXXC) and catalytic (SAM, SAH, and Sinefungin) domains using computer simulations. The results of the present study showed a potential interaction of MIC and 1,3-dimethylurea with these domains. Obviously, strong binding of MIC with DNMT1 interrupting normal methylation will lead to epigenetic alterations in the exposed humans. We suggest therefore that the MICexposed individuals surviving after 1984 disaster have excess risk of cancer, which can be attributed to alterations in their epigenome. Our findings will help in better understanding the underlying epigenetic mechanisms in humans exposed to MIC.

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There is credible evidence that the 1984–Bhopal–methyl isocyanate (MIC)–gas–exposed long-term survivors and their offspring born post-exposure are susceptible to infectious/communicable and non-communicable diseases. Bhopal’s COVID-19 fatality rate suggests that the MIC–gas tragedy survivors are at higher risk, owing to a weakened immune system and co-morbidities. This situation emboldened us to ponder over what we know, what we don’t, and what we should know about their susceptibility to COVID-19. This article aims at answering these three questions that emerge in the minds of public health officials concerning prevention strategies against COVID-19 and health promotion in the Bhopal MIC-affected population (BMAP). Our views and opinions presented in this article will draw attention to prevent and reduce the consequences of COVID-19 in BMAP. From the perspective of COVID-19 prophylaxis, the high-risk individuals from BMAP with co-morbidities need to be identified through a door-to-door visit to the severely gas-affected regions and advised to maintain good respiratory hygiene, regular intake of immune-boosting diet, and follow healthy lifestyle practices.

Background: Post burn neck contractures not only affect the movements of the neck, but also can affect the function of the lower face as well as result in possible tracheal alteration and distortion of the cervical spine. As these contractures cause major functional and cosmetic problems with resultant economic and psychosocial implications, operative correction is generally recommended, particularly in children in whom they can cause growth imbalance in the head and neck area. Aim: To determine and recommend the ideal skin cover for the post burn scar contracture release defects with regard to both functional and cosmetic outcome. Methods: Patients who were diagnosed as having post burn scar contracture of neck by clinical examination, were taken up for the study. Results: In our study, contracture release followed by skin grafting was done in 28(70%) patients, contracture release and flap cover and multiple z plasty in 6 (15%) each. 11 patients (27%) felt good, and 3 patients (11%) felt excellent on cosmetic appearance. Conclusion: TYPE A contracture, release and flap cover with supraclavicular flap is highly recommended and should be the first choice. For TYPE B contracture, Supraclavicular flap is not sufficient and has to substituted with a skin grafting. For TYPE C scar, release and skin cover with grafting is the ideal choice provided, proper post op care such as immobilization, positioning and splinting and compression therapy are followed up.

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