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 MIC- affected 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.
Highlights
Methyl isocyanate (CH3N=C=O) (MIC; CAS No 624-83-9) is a common monoisocyanate that is widely used as a precursor in carbamate pesticide production (Bucher, 1987; ATSDR, 2002)
We investigated the genotoxic effects of methyl isocyanate (MIC) in long-term survivors and their offspring born after the 1984 occurrence
Our results suggest that Exposed females (EF) and female offspring of the exposed (FOE) are more susceptible to cancer development, as compared to exposed males (EM) and male offspring of the exposed (MOE)
Summary
Asian Pacific Journal of Cancer Prevention, Vol 16, 2015 4409 emerging in vitro evidences suggest genomic instability by MIC analogs in lung (Panwar and Mishra, 2011), liver (Panwar et al, 2011) and ovary epithelial cells (Raghuram et al, 2010) that may undergo oncogenic transformation. In a five year (2006 to 2011) cross-sectional study we reported higher prevalence of lung and breast cancer (Senthilkumar et al, 2011) among the MIC-exposed long-term survivors and their offspring. Results from these epidemiological studies indicate that the cancer rate in MIC-affected population has doubled during the last 10 years. This prompted us to biomonitor the population for cytogenetic damage using micronucleus (MN) assay that suggests heightened cancer risk. Distribution of subjects with respect to smoking, alcohol consumption and tobacco-chewing was taken into account while studying its effect on MN frequency
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