Increased Micronucleus Frequency in Peripheral Blood Lymphocytes Contributes to Cancer Risk in the Methyl Isocyanate-Affected Population of Bhopal

Abstract

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.

Susceptibility of the Bhopal–methyl isocyanate (MIC)–gas–tragedy survivors and their offspring to COVID-19: What we know, what we don’t and what we should?

“…An increase in the frequency of micronucleus suggested cytogenetic damage in the EF and female offspring of the MIC-exposed substantiated transgenerational effect of MIC 13 . This evidence demonstrated MIC appears to afflict offspring born post-exposure of the survivors, particularly from the standpoint of an anomaly in the cytogenetic status.…”

“…long-term effects in the BMAP Following exposure to the toxic MIC-gas, many succumbed to death instantly, and those who survived yet suffer from agonizing prolonged health issues. Since then, the long-term effects of the exposed survivors and transgenerational repercussions in their offspring born post-exposure remain contentious [11][12][13] . For the past three decades, the government and non-government organizations have been striving to understand the MIC-induced late effects in the BMAP.…”

Cytogenetic Effects of Chronic Methylphenidate Treatment and Chronic Social Stress in Adults with Attention-Deficit/Hyperactivity Disorder

“…In our sample smoking did not increase the number of micronuclei. Results regarding the association of smoking and micronucleus frequency are inconsistent in different study population [41][42][43]. This observation might be due to intra-individual resilience or susceptibility to environmental toxic agents especially tobacco smoke and influenced by other variables in the investigated different study population [44].…”

Genotoxic and Carcinogenic Effects of Methyl Isocyanate (MIC) Reviewed on Exposed Bhopal Population and Future Perspectives for Assessment of Long-Term MIC-Effect

“…The prevalence of genetic abnormalities in 100% cases after 27 years from the disaster has not been discussed with sufficient information. The same group, after reporting chromosome data, has reported micronuclei frequency in MIC exposed population as an indicator of cancer incidence; however, the report has not stated the incidence of cancer in their hospital registry [42].…”