title: 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 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.
authors.affiliation: Clinical Cytogenetics Laboratory, Department of Research, Jawaharlal Nehru Cancer Hospital and Research Centre, Bhopal, Madhya Pradesh, India E-mail : sengenetics@gmail.com.
authors.forename: Chinnu Sugavanam
authors.initials: CS
authors.lastname: Senthilkumar
authors.forename: Sameena
authors.initials: S
authors.lastname: Akhter
authors.forename: Tahir Mohiuddin
authors.initials: TM
authors.lastname: Malla
authors.forename: Nand Kishore
authors.initials: NK
authors.lastname: Sah
authors.forename: Narayanan
authors.initials: N
authors.lastname: Ganesh
mesh_terms: D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D055908:Bhopal Accidental Release; D016022:Case-Control Studies; D048750:Cell Nucleus Division; D002648:Child; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D017953:Isocyanates / Q000633:toxicity*; D008019:Life Style; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D018811:Maternal Exposure; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests / Q000379:methods; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics; D018812:Paternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D017741:Survivors; D014030:Tobacco, Smokeless / Q000009:adverse effects; D055815:Young Adult
chemical_list: D017953:Isocyanates; C008461:methyl isocyanate