Contents lists available at ScienceDirect Mutat Res Gen Tox En journal homepage: www.elsevier.com/locate/gentox Cytogenetic changes in the Bhopal population exposed to methyl isocyanate (MIC) in 1984: Then and 30 years later Bani Bandana Ganguly, Shouvik Mandala MGM Center for Genetic Research & Diagnosis, MGM New Bombay Hospital, Navi Mumbai, India ARTICLE INFO Keywords: Methyl isocyanate Cytogenetic screening Chromosomal aberrations Sister chromatid exchanges Cell-cycle kinetics ABSTRACT Following the 1984 Bhopal methyl isocyanate (MIC) Bhopal gas disaster, genetic alterations were sporadically reported on small cohorts. However, the outcome of the multi-center cytogenetic screening conducted at that time remains unknown and no follow-up studies on the long-term effects of MIC exposure have been published. The present work examines genetic changes in the exposed population,with the aim of identifying any long-term effects of MIC. G-Banded metaphases were studied in lymphocytes of 130 individuals. Chromosomal aberrations (CA) were broadly grouped as abnormal cells (Abc), aberrations (Abn), and aberration/abnormal cell (Abn/Abc). From the previous multi-center screening, 946 records were retrieved, from which CA, sister chromatid ex- changes (SCE), and cell-cycle kinetics (RI) were computed. In our analysis of the previous study, Abc and Abn were higher in the moderately and severely exposed groups than in the unexposed population. Abc appeared uniform in all groups of the present study, although Abn and Abn/Abc were higher in the exposed groups. Aberrations were now significantly higher in the unexposed and moderately exposed groups than in the previous screening. Although Abn and Abc now appeared lower in severely exposed subjects, the Abn/Abc ratio was higher, perhaps due to more rearrangements and damage in a smaller number of Abc. This result may be at- tributed to differences between the methods used in the studies, then and now. Elevated SCEs and reduced RI were seen in the severely exposed population shortly after exposure, and stable/clonal rearrangements were seen 30 y later. Follow-up of index cases and their progenies is needed. 1. Introduction Environmental factors may cause genetic damage to individuals and their descendants [1–5]. The poor are especially likely to be exposed to environmental pollution, both at home and at work. Persons who lived near the Union Carbide India Ltd. (UCIL), Bhopal pesticide manu- facturing plant were severely affected by the 1984 methyl isocyanate (MIC) gas leak disaster. Medical investigations, including autopsies of the victims and subsequent monitoring of the survivors, established the severity of MIC’s acute toxicity [6–9]. Medical management was em- pirical, since no specific treatments for MIC poisoning were known. Prior information concerning MIC effects in the exposed population was limited to a single publication from 1964 [10]. The Bhopal disaster stimulated the scientific community to further study MIC toxicity [11,12]. Indian scientists and doctors continued research on the MIC- victims [8,13–16] and the Indian Council of Medical Research (ICMR) continued monitoring of the survivors’ health and screening of the population [8,17]. Genetic studies of the survivors (despite shortcoming in study de- sign, sample selection, and assessment of exposure status) demonstrated the clastogenicity of MIC. In- and out-migration shortly after the dis- aster became a persistent confounder in screening of the MIC-exposed population [18]. ICMR assigned a unique identification number to each exposed family in the stratified exposed zones, and this has been maintained. Multi-center genetic screening was conducted by ICMR during 1985–1989; however, the research has not been published (the corresponding author of this article was involved in that screening, through the Kolkata Center). The protocol of that screening is men- tioned briefly in the Methods section of this article. The genotoxic potential of MIC has been assessed in vitro and in vivo [19–23], as reviewed recently [24]. Several such review reports are available in the literature on the disaster; all are based on the initial reports only. There has been no further systematic investigation of the MIC-exposed population. Since 1984, at least two more generations have been added, and many of the exposed individuals have become old. Although geno toxicity of MIC was assessed in the exposed popu- lation shortly after the disaster, there has been no further investigation of possible long-term effects. To address this knowledge gap, ICMR has sponsored an investigation of the current genetic conditions of the ex- posed cases, as a pilot study. As part of this project, the present study http://dx.doi.org/10.1016/j.mrgentox.2017.10.004 Received 18 July 2017; Received in revised form 9 October 2017; Accepted 11 October 2017 E-mail addresses: mgmgeneitclab@yahoo.com, bani.b.ganguly@gmail.com (B.B. Ganguly). Mutat Res Gen Tox En 824 (2017) 9–19 Available online 13 October 2017 1383-5718/ © 2017 Elsevier B.V. All rights reserved. MARK