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 accidentsin recent decades. We investigated the genotoxic effects of MIC in long-term survivors and their offspring bornafter the 1984 occurrence. There are a few cytogenetic reports showing genetic damage in the MIC-exposedsurvivors, but there is no information about the associated cancer risk. The same is true about offspring. For thefirst 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 MICaffectedand 46 controls) from Bhopal and various regions of India were studied taking gender and age intoconsideration. 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 lifestylevariabilities (smoking, alcohol consumption and tobacco-chewing) were investigated. Our observations showedrelatively 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, femaleoffspring of the exposed (FOE) also suffered higher BNMN and MNL (P<0.05) than in controls. A significantreduction in NDI (P<0.05) was found only in EF. The affected group of non-smokers and non-alcoholics featureda 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) thanthe non-chewers. Amongst the affected, smoking and alcohol consumption were not associated with statisticallysignificant differences in BNMN, MNL and NDI. Nevertheless, tobacco-chewing had a preponderant effect withrespect to MNL. A reasonable correlation between MNL and lifestyle habits (smoking, alcohol consumption andtobacco-chewing) was observed only in the controls. Our results suggest that EF and FOE are more susceptibleto cancer development, as compared to EM and MOE. The genotoxic outcome detected in FOE reflects theirparental exposure to MIC. Briefly, the observed cytogenetic damage to the MIC-affected could contribute tocancer risk, especially in the EF and FOE.

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