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Frequency of micronuclei in population of Bhopal exposed to methyl isocyanate in 1984

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Abstract

Micronuclei represent whole chromosome or large acentric fragments lagging behind the ana-telophasic separation of cell division. However, it progresses towards completion of karyokinesis and eventually gets included in one of the two daughter cells through cytokinesis. The frequency of micronuclei was estimated in 107 subjects exposed to methyl isocyanate (MIC) gas 30-years post-disaster and compared with 35 unexposed subjects of similar socio-cultural background from the same geographical region. Ethical approval and participants’ informed consent were obtained, and quality issues were validated prior to the proposed investigation. Peripheral blood was collected for each participant from their residence and transported to Mumbai for technical processing and cytogenetic analysis. Replicate cultures with 0.5 ml of whole blood were stimulated in 5 ml of serum supplemented RPMI1640 medium and maintained at 37°C for 72 h. The cells were dropped onto chilled slides following standard harvesting schedule, air dried and stained in Giemsa. Microscopic observation of 1000 cells for each subject has recognized lymphocyte cells (MNC) with micronucleus (MN). The ratio of MN and MNC indicated number of micronuclei per micronucleated cell. Statistical analysis revealed exposure related incidences of MN, MNC and MN/MNC, which was significant (p < 0.05) when compared with unexposed population and/or between moderate and severe exposure status (MN) of the population. Age-related MNC-incidence was significant between adult and childhood exposure to MIC gas. The differences of MN-incidences in the three severely exposure-zones (S1, S2, and S7) were significantly higher than the unexposed zones (C14, C16). The incidence of MN was consistent with our earlier study on chromosome aberrations detected in the same population 30-years post-disaster. However, the MN/CA incidences cannot be directly linked to MIC-exposure of 1984 owing to contribution of several confounding factors over 30 years. Nevertheless, the study could be considered as a low-cost tool but useful for estimation of DNA-damage in risk-assessment.

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References

  1. Countryman PJ, Heddle JA. The production of micronuclei from chromosome aberration in irradiated cultures of human lymphocytes. Mutat Res. 1976;41:321–32.

    Article  CAS  Google Scholar 

  2. Cullinan P, Acquilla SD, Dhara VR. Long term morbidity in survivors of the 1984 Bhopal gas leak. Natl Med J India. 1996;9:5–10.

    CAS  PubMed  Google Scholar 

  3. Cullinan P, Acquilla SD, Dhara VR. Respiratory morbidity 10 years after the Union Carbide gas leak at Bhopal: a cross-sectional survey. Br Med J. 1997;314:338–42.

    Article  CAS  Google Scholar 

  4. Dhara VR, Acquilla SD. Distance of residence in 1984 may be used as exposure surrogate for the Bhopal disaster. Ind J Med Res. 2012;136:1060–1.

    Google Scholar 

  5. Dhara VR, Acquilla SD. Regarding distance of residence in 1984 may be used as exposure surrogate for the Bhopal disaster—further observations on post-disaster epidemiology. Ind J Med Res. 2013;138:270–2.

    Google Scholar 

  6. Dhara VR, Dhara R, Acquilla SD, Cullinan P. Personale-exposure and long-term health effects in survivors of the Union Carbide Disaster at Bhopal. Environ Health Perspect. 2002;110:487–500.

    Article  CAS  Google Scholar 

  7. EHC. Environmental Health Criteria 46. Guidelines for the study of genetic effects in human populations. Geneva: World Health Organization; 1985.

    Google Scholar 

  8. EHP. Environmental Health Perspectives. 1987;72:3–198.

  9. Fenech M, Morley AA. The effect of spontaneous and induced micronuclei. Mutat Res. 1985;148:99–105.

    Article  CAS  Google Scholar 

  10. Ganguly BB. Cell division, chromosomal aberration and micronuclei formation in human peripheral blood lymphocytes: effect of stannic chloride on donor’s age. Biol Trace Element Res. 1991;38:55–62.

    Article  Google Scholar 

  11. Ganguly BB. Cell division, chromosomal damage and micronucleus formation in peripheral lymphocytes of healthy donors: related to donor’s age. Mutat Res. 1993;295:135–48.

    Article  CAS  Google Scholar 

  12. Ganguly BB. Exposure assessment of chemical incidents: lesson from methyl isocyanate (MIC) gas disaster. Environ Toxicol Stud J. 2017;1(1):6.

    Google Scholar 

  13. Ganguly BB. Small molecule inhibitors of epigenetic mutations as compelling drug targets for myelodysplastic syndromes. Curr Cancer Drug Targets. 2017;17(7):586–602. https://doi.org/10.2174/15680096170330145002.

    Article  CAS  Google Scholar 

  14. Ganguly BB. Exposure index of methyl isocyanate (MIC) gas disaster and a comprehensive spectrum of cytogenetic analysis after 30 years. Environ Sci Pollut Res. 2019;26:18208–29. https://doi.org/10.1007/s11356-019-04439-0.

    Article  CAS  Google Scholar 

  15. Ganguly BB. Effect of exposure-age on chromosomal rearrangements in methyl isocyanate (MIC) gas exposed survivors. Atlas of Science. https://atlasofscience.org/effect-of-exposure-age-on-chromosomal-rearrangements-in-methyl-isocyanate-mic-gas-exposed-survivors/. Accessed 26 Sept 2019.

  16. Ganguly BB, Kadam NN. Mutations of myelodysplastic syndromes (MDS): an update. Mutat Res. 2016;769:47–62.

    Article  CAS  Google Scholar 

  17. Ganguly BB, Mandal S. Cytogenetic changes in the Bhopal population exposed to methyl isocyanate (MIC) in 1984: then and 30 years later. Mutat Res Genet Toxicol Environ. 2017;824:9–19. https://doi.org/10.1016/j.mrgentox.2017.10.004.

    Article  CAS  Google Scholar 

  18. Ganguly BB, Mandal S, Kadam NN, Banerjee D, Chandra S, Dolai TK, Agarwal MB. Experience of conventional cytogenetics in elderly cytopenic Indian patients suspected with myelodysplastic syndromes. Blood. 2016;128:5488 (ASH 2016 Abstract).

    Article  Google Scholar 

  19. Ganguly BB, Mandal S, Kadam NN. Genotoxic and carcinogenic effects of methyl isocyanate (MIC) reviewed on exposed Bhopal population and future perspectives for assessment of long-term MIC-effect. J Environ Anal Toxicol. 2017;7:3. https://doi.org/10.4172/2161-0525.1000452.

    Article  Google Scholar 

  20. Ganguly BB, Mandal S, Kadam NN. Spectrum of health condition in Methyl isocyanate (MIC)-exposed survivors measured after 30 years of disaster. Environ Sci Pollut Res. 2018;25(5):4963–73. https://doi.org/10.1007/s11356-017-0865-6.

    Article  CAS  Google Scholar 

  21. Ganguly BB, Mandal S, Banerjee N, Kadam NN, Abbi R. Effect of age at exposure on chromosome abnormalities in MIC-exposed Bhopal population detected 30 years post-disaster. Mutat Res Fund Mol Mech Mutagen. 2018;809:32–50.

    Article  CAS  Google Scholar 

  22. Ghosh BB. Alterations in Structure and Behaviour of Chromosomes and Certain Cellular Components Induced by Heavy Metal. Ph.D. Thesis. 1988. University of Calcutta, Kolkata, India.

  23. Ghosh BB, Sengupta S, Roy A, maity S, Ghosh S, Talukder G, Sharma A. Cytogenetic studies in human populations exposed to gas leak at Bhopal. Environ Health Perspect. 1990;86:323–6.

    Article  CAS  Google Scholar 

  24. Ghosh BB, Talukder G, Sharma A. Frequency of micronuclei induced in peripheral lymphocytes by trimethyltin chloride. Mutat Res. 1990;245:33–9.

    Article  CAS  Google Scholar 

  25. ICMR Technical Report Technical report on Population based long term clinical studies. In: Health effects of the toxic gas leak from Union Carbide methyl isocyanate plant in Bhopal (1984–1992) (Sriramachari S, ed). 2008. Indian Council of Medical Research, New Delhi, India.

  26. Kimmerle G, Eben A. Toxicity of methyl isocyanate and how to determine the quantity of air. Arch Toxicol. 1964;20:235–41.

    CAS  Google Scholar 

  27. Léonard A, Deknudt G, Léonard ED. Persistence of chromosome aberrations in an accidentally irradiated subject. Radiat Prot Dosim. 1988;22:55–7.

    Google Scholar 

  28. Lucas JN, Poggensee M, Straume T. The persistence of chromosome translocations in a radiation worker accidentally exposed to tritium. Cytogenet Cell Genet. 1992;60:255–6.

    Article  CAS  Google Scholar 

  29. Michie CA, McLean A, Alcock C, Beverley PC. Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature. 1992;360(6401):264–5.

    Article  CAS  Google Scholar 

  30. Ramalho AT, Curado MP, Natarajan AT. Lifespan of human lymphocytes estimated during a six year cytogenetic follow-up of individuals accidentally exposed in the 1987 radiological accident in Brazil. Mutat Res. 1995;331(1):47–54.

    Article  CAS  Google Scholar 

  31. Röth A, Yssel H, Pène J, Chavez EA, Schertzer M, Lansdorp PM, Spits H, Luiten RM. Telomerase levels control the lifespan of human T lymphocytes. Blood. 2003;102:849–57.

    Article  Google Scholar 

  32. Savage JR. Classification and relationships of induced chromosomal structural changes. J Med Genet. 1976;b13(2):103–22.

    Article  Google Scholar 

  33. Speicher MR, Antonarakis SE, Vogel Motulsky AG, Human Motulsky’s. Genetics: problems and approaches. 4th ed. Berlin: Springer; 2010. https://doi.org/10.1007/978-3-540-37654-5.

    Book  Google Scholar 

  34. Stich FH, Curtis JR, Parida BB. Application of the micronucleus test to exfoliated cells of higher cancer risk groups: tobacco chewers. Int J Cancer. 1982;30:553–9.

    Article  CAS  Google Scholar 

  35. Technical Report. Technical Report on Population based long term epidemiological studies Part II (1996–2010). 2013. Health Effects of the toxic gas leak from the Union Carbide methyl isocyanate plant in Bhopal. Centre for Rehabilitation Studies, Government of Madhya Pradesh, Bhopal and National Institute for Research in Environmental Health, Bhopal, Madhya Pradesh, India.

  36. Varma DR, Guest I. The Bhopal accident and methyl isocyanate toxicity. J Toxicol Environ Health. 1993;40(4):513–29.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors wish to acknowledge financial support (partial) of Indian Council of Medical Research (Grant Number: ICMR-65/BBG-1/NCD-II & NIREH/IMP/BBG/2013/01) and Mahatma Gandhi Mission Trust extended for this publication. The authors also acknowledge the administrative support of ICMR-National Institute for Research in Environmental Health, Bhopal, and technical support of Ms. Poonam Pawar.

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Authors and Affiliations

  1. MGM Center for Genetic Research and Diagnosis, Vashi Sector 3, Navi Mumbai, 400703, India

    Bani Bandana Ganguly & Shouvik Mandal

  2. MGM Institute of Health Sciences, Navi Mumbai, India

    Bani Bandana Ganguly & Nitin N. Kadam

  3. MGM Dental College and Hospital, Navi Mumbai, India

    Shouvik Mandal

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  1. Bani Bandana Ganguly
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Ganguly, B.B., Mandal, S. & Kadam, N.N. Frequency of micronuclei in population of Bhopal exposed to methyl isocyanate in 1984. Nucleus 62, 269–275 (2019). https://doi.org/10.1007/s13237-019-00300-4

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