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Increased Micronucleus Frequency in Peripheral Blood Lymphocytes Contributes to Cancer Risk in the Methyl Isocyanate-Affected Population of Bhopal

  • Senthilkumar, Chinnu Sugavanam (Clinical Cytogenetics Laboratory, Department of Research, Jawaharlal Nehru Cancer Hospital & Research Centre) ;
  • Akhter, Sameena (Clinical Cytogenetics Laboratory, Department of Research, Jawaharlal Nehru Cancer Hospital & Research Centre) ;
  • Malla, Tahir Mohiuddin (Clinical Cytogenetics Laboratory, Department of Research, Jawaharlal Nehru Cancer Hospital & Research Centre) ;
  • Sah, Nand Kishore (TNB College, TM Bhagalpur University) ;
  • Ganesh, Narayanan (Clinical Cytogenetics Laboratory, Department of Research, Jawaharlal Nehru Cancer Hospital & Research Centre)
  • Published : 2015.06.03

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.

Keywords

References

  1. Abdullah N, Orta T (2012). Relationship between malignant melanoma and chromosome damage in human peripheral blood lymphocytes. Asian Pac J Cancer Prev, 13, 5229-32. https://doi.org/10.7314/APJCP.2012.13.10.5229
  2. Albertini RJ, Anderson D, Douglas GR, et al (2000). IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. Mutat Res, 463, 111-72. https://doi.org/10.1016/S1383-5742(00)00049-1
  3. Andersson N, Ajwani MK, Mahashabde S, et al (1990). Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal. Br J Ind Med, 47, 553-58.
  4. Anwar WA, Gabal MS (1991). Cytogenetic study in workers occupationally exposed to mercury fulminate. Mutagenesis, 6, 189-92. https://doi.org/10.1093/mutage/6.3.189
  5. ATSDR (2002). Methyl isocyanate (CAS#624-83-9). ToxFAQsTM. Emergency department management, Agency for toxic substances and disease registry, U.S. Department of health and human services, Atlanta, GA, 2002. Available at URL: http://www.atsdr.cdc.gov/toxfaqs/tf.asp?id=629&tid=116 (Assessed on 8.6.2014)
  6. Balamuralikrishnan B, Balachandar V, Sureshkumar S, et al (2012). Evaluation of chromosomal alteration in electrical workers occupationally exposed to low frequency of electro magnetic field (EMFs) in Coimbatore population, India. Asian Pac J Cancer Prev, 13, 2961-6. https://doi.org/10.7314/APJCP.2012.13.6.2961
  7. Bates MN, Hamilton JW, LaKind JS, et al (2005). Workgroup report: biomonitoring study design, interpretation, and communication-lessons learned and path forward. Environ Health Perspect, 113, 1615-21. https://doi.org/10.1289/ehp.8197
  8. Bessac BF, Sivula M, Von Hehn CA, et al (2009). Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J, 23, 1102-14. https://doi.org/10.1096/fj.08-117812
  9. Bhalli JA, Khan QM, Haq MA, et al (2006). Cytogenetic analysis of Pakistani individuals occupationally exposed to pesticides in a pesticide production industry. Mutagenesis, 21, 143-8. https://doi.org/10.1093/mutage/gel009
  10. Boffetta P, Vander Hel O, Norppa H, (2007). Chromosomal aberrations and cancer risk: results of a cohort study from central europe. Am J Epidemiol, 165, 36-43.
  11. Bolognesi C, Creus A, Wegman PO, et al (2011). Micronuclei and pesticide exposure. Mutagenesis, 26, 19-26. https://doi.org/10.1093/mutage/geq070
  12. Bolognesi C, Merlo F, Rabboni R, et al (1997).Cytogenetic biomonitoring in traffic police workers: micronucleus test in peripheral blood lymphocytes. Environ Mol Mutagen, 30, 396-402. https://doi.org/10.1002/(SICI)1098-2280(1997)30:4<396::AID-EM4>3.0.CO;2-H
  13. Bolognesi C, Parrini M, Bonassi S, et al (1993). Cytogenetic analysis of a human population occupationally exposed to pesticides. Mutat Res, 285, 239-49. https://doi.org/10.1016/0027-5107(93)90112-S
  14. Bolognesi C, Perrone E, Landini E (2002). Micronucleus monitoring of a floriculturist population from Western Liguria, Italy. Mutagenesis, 17, 391-7. https://doi.org/10.1093/mutage/17.5.391
  15. Bonassi S, El-Zein R, Bolognesi C, et al (2011). Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis, 26, 93-100. https://doi.org/10.1093/mutage/geq075
  16. Bonassi S, Hagmar L, Stromberg U, et al (2000). Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. Cancer Res, 60, 1619-25.
  17. Bonassi S, Neri M, Lando C, et al (2003). Effect of smoking habit on the frequency of micronuclei in human lymphocytes: Results from the Human MicroNucleus project. Mutat Res, 543, 155-166. https://doi.org/10.1016/S1383-5742(03)00013-9
  18. Bonassi S, Norppa H, Ceppi M, et al (2008). Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries. Carcinogenesis, 29, 1178-83. https://doi.org/10.1093/carcin/bgn075
  19. Bonassi S, Znaor A, Ceppi M, et al (2007). An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis, 28, 625-31.
  20. Bucher JR (1987). Methyl isocyanate: A review of health effects research since Bhopal. Fund Appl Toxicol, 9, 367-79. https://doi.org/10.1016/0272-0590(87)90019-4
  21. Bucher JR, Uraih L (1989). Carcinogenicity and pulmonary pathology associated with a single 2-hour inhalation exposure of laboratory rodents to methyl isocyanate. J Nat Cancer Inst, 81, 1586-7. https://doi.org/10.1093/jnci/81.20.1586
  22. Calvert GM, Talaska G, Mueller CA, et al (1998). Genotoxicity in workers exposed to methyl bromide. Mutat Res, 417, 115-28. https://doi.org/10.1016/S1383-5718(98)00105-3
  23. Carter SB (1967). Effects of cytochalasins on mammalian cells. Nature, 213, 261-4. https://doi.org/10.1038/213261a0
  24. Conner MK, Rubinson HF, Ferguson JS (1987). Evaluation of sister chromatid exchange and cytogenicity in murine tissues in vivo and lymphocytes in vitro following methyl isocyanate exposure. Env Health Perspectives, 72, 115-21.
  25. Costa C, Teixeira JP, Silva S, et al (2006). Cytogenetic and molecular biomonitoring of a Portuguese population exposed to pesticides. Mutagenesis, 21, 343-50. https://doi.org/10.1093/mutage/gel039
  26. da Cruz AD, McArthur AG, Silva CC, et al (1994). Human micronucleus counts are correlated with age, smoking, and cesium-137 dose in the Goiânia (Brazil) radiological accident. Mutat Res, 313, 57-68. https://doi.org/10.1016/0165-1161(94)90033-7
  27. Da Silva Augusto LG, Lieber SR, Ruiz MA et al (1997). Micronucleus monitoring to assess human occupational exposure to organochlorides. Environ Mol Mutagen, 29, 46-52. https://doi.org/10.1002/(SICI)1098-2280(1997)29:1<46::AID-EM6>3.0.CO;2-B
  28. Das RK, Das BC (1992). Genotoxicity of gudakhu a tobacco preparation II. In habitual users. Food Chem Toxicol, 12, 1045-52.
  29. De Boeck M, Lardau S, Buchet JP, et al (2000). Absence of significant genotoxicity in lymphocytes and urine from workers exposed to moderate levels of cobalt-containing dust: a cross-sectional study. Environ Mol Mutagen, 36, 151-60. https://doi.org/10.1002/1098-2280(2000)36:2<151::AID-EM10>3.0.CO;2-V
  30. Declaration of Helsinki (DoH) (2000). World Medical Association. Available from URL: http://www.wma.net/[accessed on June 7, 2007 and February 18, 2010].
  31. Deo MG, Gangal S, Bhisey AN, et al (1987). Immunological, mutagenic and genotoxic investigations in gas exposed population of Bhopal. Indian J Med Res, 86, 63-76.
  32. Dhara VR, Dhara R (2002). The Union Carbide disaster in Bhopal: a review of health effects. Arch Environ Health, 57, 391-404. https://doi.org/10.1080/00039890209601427
  33. Dhara VR, Kriebel D (1993). The Bhopal gas disaster: It's not too late for sound epidemiology. Arch Environ Health, 48, 436-7. https://doi.org/10.1080/00039896.1993.10545966
  34. Di Giorgio C, De Méo MP, Laget M, et al (1994). The micronucleus assay in human lymphocytes: screening for inter-individual variability and application to biomonitoring. Carcinogenesis, 15, 313-7. https://doi.org/10.1093/carcin/15.2.313
  35. Dikshit RP, Kanhere S (1999). Cancer patterns of lung, oropharynx and oral cavity cancer in relation to gas exposure at Bhopal. Cancer Causes and Control, 10, 627-36. https://doi.org/10.1023/A:1008930220304
  36. Donmez-Altuntas H, Bitgen N (2012).Evaluation of the genotoxicity and cytotoxicity in the general population in Turkey by use of the cytokinesis-block micronucleus cytome assay. Mutat Res, 748, 1-7. https://doi.org/10.1016/j.mrgentox.2012.05.013
  37. Eastmond DA, Tucker JD (1989). Identification of aneuploidyinducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody. Environ Mol Mutagen, 13, 34-43. https://doi.org/10.1002/em.2850130104
  38. El-Zein R, Vral A, Etzel CJ (2011). Cytokinesis-blocked micronucleus assay and cancer risk assessment. Mutagenesis, 26, 101-6. https://doi.org/10.1093/mutage/geq071
  39. Ennever FK, Rosenkranz HS (1987). Evaluating the potential for genotoxic carcinogenicity of methyl isocyanate. Toxicol Appl Pharmacol, 91, 502-5. https://doi.org/10.1016/0041-008X(87)90073-1
  40. Erdem MG, Cinkilic N, Vatan O, et al (2012). Genotoxic and anti-genotoxic effects of vanillic acid against mitomycin c-induced genomic damage in human lymphocytes in vitro. Asian Pac J Cancer Prev, 13, 4993-8. https://doi.org/10.7314/APJCP.2012.13.10.4993
  41. Fenech M (1993). The cytokinesis-block micronucleus technique: A detailed description of the method and its application to genotoxicity studies in human populations. Muta Res, 285, 35-44. https://doi.org/10.1016/0027-5107(93)90049-L
  42. Fenech M (1998). Important variables that influence base-line micronucleus frequency in cytokinesis-blocked lymphocytes a biomarker for DNA damage in human populations. Mutat Res, 404, 155-65. https://doi.org/10.1016/S0027-5107(98)00109-2
  43. Fenech M (2000). The in vitro micronucleus technique. Mutat Res, 455, 81-95. https://doi.org/10.1016/S0027-5107(00)00065-8
  44. Fenech M, Bonassi S (2011). The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes. Mutagenesis, 26, 43-49. https://doi.org/10.1093/mutage/geq050
  45. Fenech M, Chang WP, Kirsch-Volders M, et al (2003). HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res, 534, 65-75. https://doi.org/10.1016/S1383-5718(02)00249-8
  46. Fenech M, Holland N, Chang WP, et al (1999). The HUman MicroNucleus project-an international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res, 428, 271-83. https://doi.org/10.1016/S1383-5742(99)00053-8
  47. Fenech M, Morley AA (1985a). Measurement of micronuclei in lymphocytes. Mutat Res, 147, 29-36. https://doi.org/10.1016/0165-1161(85)90015-9
  48. Fenech M, Morley AA (1985b). The effect of donor age on spontaneous and induced micronuclei. Mutat Res, 148, 99-105. https://doi.org/10.1016/0027-5107(85)90212-X
  49. Fenech M, Morley AA (1986). Cytokinesis-block micronucleus method in human lymphocytes: effect of in vivo ageing and low dose X irradiation. Mutat Res, 161, 193-8. https://doi.org/10.1016/0027-5107(86)90010-2
  50. Fenech M, Neville S, Rinaldi J (1994). Sex is an important variable affecting spontaneous micronucleus frequency in cytokinesis-blocked lymphocytes. Mutat Res, 313, 203-7. https://doi.org/10.1016/0165-1161(94)90050-7
  51. Fenech M, Rinaldi J (1994). The relationship between micronuclei in human lymphocytes and plasma levels of vitamin C, vitamin E, vitamin B12 and folic acid. Carcinogenesis, 15, 1405-11. https://doi.org/10.1093/carcin/15.7.1405
  52. Figgs LW, Holland NT, Rothman N, et al (2000). Increased lymphocyte replicative index following 2, 4-dichlorophenoxyacetic acid herbicide exposure. Cancer Causes & Control, 11, 373-80. https://doi.org/10.1023/A:1008925824242
  53. Gajski G, Geric M, Oreščanin V, et al (2013). Cytogenetic status of healthy children assessed with the alkaline comet assay and the cytokinesis-block micronucleus cytome assay. Mutat Res, 750, 55-62. https://doi.org/10.1016/j.mrgentox.2012.09.011
  54. Ganesh N, Sanyal B, Panday RK, et al (2005). Cancer patterns among MIC gas survivors and their offspring. Health administrator, 17, 50-58.
  55. Gassert T, Mackenzie C, Muir KM, et al (1986). Long term pathology of lung, eye, and other organs following acute exposure of rats to methyl isocyanate. Lancet, 2, 1403.
  56. George A, Dey R, Bhuria V, et al (2014). Nuclear anomalies, chromosomal aberrations and proliferation rates in cultured lymphocytes of head and neck cancer patients. Asian Pac J Cancer Prev, 15, 1119-23. https://doi.org/10.7314/APJCP.2014.15.3.1119
  57. Ghosh BB, Sengupta S, Roy A, et al (1990). Cytogenetic studies in human populations exposed to gas leak at Bhopal, India. Environ Health Perspectives, 86, 323-26. https://doi.org/10.1289/ehp.9086323
  58. Gomez-Arroyo S, Diaz-Sanchez Y, Meneses-Perez MA, et al (2000). Cytogenetic biomonitoring in a Mexican floriculture workers group exposed to pesticides. Mutat Res, 466, 117-24. https://doi.org/10.1016/S1383-5718(99)00231-4
  59. Goswami HK (1986). Cytogenetic effects of methyl isocyanate exposure in Bhopal. Hum Genet, 74, 42-45.
  60. Goswami HK, Chandolkar M, Bhattacharya K, et al (1990). Search for chromosomal variations among gas exposed persons in Bhopal. Hum Genet, 84, 172-76.
  61. Hagmar L, Bonassi S, Stromberg U, et al (1998). Chromosomal aberrations in lymphocytes predict human cancer: A report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res, 58, 4117-21.
  62. Hagmar L, Brogger A, Hansteen IL, et al (1994). Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic Study Group on the health risk of chromosome damage. Cancer Res, 54, 2919-22.
  63. Hagmar L, Stromberg U, Bonassi S, et al (2004). Impact of types of lymphocyte chromosomal aberrations on human cancer risk: Results from Nordic and Italian cohorts. Cancer Res, 64, 2258-63. https://doi.org/10.1158/0008-5472.CAN-03-3360
  64. Hagmar L, Stromberg U, Tinnerberg HK, et al (2001). The usefulness of cytogenetic biomarkers as intermediate endpoints in carcinogenesis. Int J Hyg Environ Health, 204, 43-7. https://doi.org/10.1078/1438-4639-00071
  65. Hogstedt B (1984). Micronuclei in lymphocytes with preserved cytoplasm: a method for assessment of cytogenetic damage in man. Mutat Res, 130, 63-72. https://doi.org/10.1016/0165-1161(84)90007-4
  66. Hogstedt B, Gullberg B, Hedner K, et al (1983). Chromosome aberrations and micronuclei in bone marrow cells and peripheral blood lymphocytes in humans exposed to ethylene oxide. Hereditas, 98, 105-13.
  67. Hook EB (1982). International commission for protection against environmental mutagens and carcinogens (ICPEMC) working paper 5/2: perspectives in mutation epidemiology: epidemiologic and design aspects of studies of somatic chromosome breakage and sister chromatid exchange. Mutat Res, 99, 373-382. https://doi.org/10.1016/0165-1110(82)90053-7
  68. HSFS (2002). Methyl isocyanate. RTK 1270, Department of Health and Senior Services, Hazardous substance fact sheet, New Jersey. Available from URL: http://www.nj.gov/health/eoh/rtkweb/documents/fs/1270.pdf (Assessed on 8.6.2014)
  69. ICMR (2004). Health effects of the toxic gas leak from the union carbide Methyl isocyanate plant in Bhopal, Technical report on population based long term clinical studies (1985-1994). Indian Council of Medical Research. New Delhi, India. (Cited August 8, 2012), Available from URL: http://icmr.nic.in/pinstitute/nireh.htm
  70. ICMR (2006). Ethical guidelines for biomedical research on human participants. Indian Council of Medical Research. New Delhi, India. (accessed on November 3, 2008 and February 18, 2010), Available from URL: http://icmr.nic.in/ethical_guidelines.pdf
  71. Ishikawa H, Ishikawa T, Yamamoto H, et al (2007). Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B and ALDH2 gene polymorphisms. Mutat Res, 615, 134-42. https://doi.org/10.1016/j.mrfmmm.2006.11.026
  72. Ishikawa H, Miyatsu Y, Kurihara K, et al (2006). Geneenvironmental interactions between alcohol-drinking behavior and ALDH2 and CYP2E1 polymorphisms and their impact on micronuclei frequency in human lymphocytes. Mutat Res, 594, 1-9. https://doi.org/10.1016/j.mrfmmm.2005.07.005
  73. Ishikawa H, Yamamoto H, Tian Y, et al (2003). Effects of ALDH2 gene polymorphisms and alcohol drinking behavior on micronuclei frequency in non-smokers. Mutat Res, 541, 71-80. https://doi.org/10.1016/S1383-5718(03)00179-7
  74. Joksic G, Vidakovic A, Spasojevic-Tisma V (1997). Cytogenetic monitoring of pesticide sprayers. Environ Mol Mutagen, 75, 113-8.
  75. Kapoor R (1991). Fetal loss and contraceptive acceptance among the Bhopal gas victims. Soc Biol, 38, 242-8.
  76. Karol MH, Taskar S, Gangal S, et al (1987). The antibody response to Methyl isocyanate: experimental and clinical findings. Env Health Perspectives, 72, 169-75. https://doi.org/10.1289/ehp.8772169
  77. Kim JS, Kim YJ, Kim TY, et al (2005). Association of ALDH2 polymorphism with sensitivity to acetaldehyde-induced micronuclei and facial flushing after alcohol intake. Toxicol, 210, 169-74. https://doi.org/10.1016/j.tox.2005.01.016
  78. Kumar A, Yadav A, Giri SK, et al (2011). Influence of GSTM1 and GSTT1 genotypes and confounding factors on the frequency of sister chromatid exchange and micronucleus among road construction workers. Chemosphere, 84, 564-70. https://doi.org/10.1016/j.chemosphere.2011.04.008
  79. Liao YP, Zhang D, Sun Z, et al (2014). A modified protocol for the cytokinesis-block micronucleus (CBMN) assay using whole human blood. Fudan Univ J Med Sci, 41, 395-9.
  80. Luster MI (1986). Immunotoxicity studies on mice exposed to methyl isocyanate. Toxicol Appl Pharmacology, 86, 140-4. https://doi.org/10.1016/0041-008X(86)90407-2
  81. Maffei F, Angelini S, Forti GC, et al (2002a). Micronuclei frequencies in hospital workers occupationally exposed to low levels of ionizing radiation: influence of smoking status and other factors. Mutagenesis, 17, 405-9. https://doi.org/10.1093/mutage/17.5.405
  82. Maffei F, Fimognari C, Castelli E, et al (2000). Increased cytogenetic damage detected by FISH analysis on micronuclei in peripheral lymphocytes from alcoholics. Mutagenesis, 15, 517-23. https://doi.org/10.1093/mutage/15.6.517
  83. Maffei F, Forti GC, Castelli E, et al (2002b). Biomarkers to assess the genetic damage induced by alcohol abuse in human lymphocytes. Mutat Res, 514, 49-58. https://doi.org/10.1016/S1383-5718(01)00318-7
  84. Main PA, Thomas P, Angley MT, et al (2015). Lack of evidence for genomic instability in autistic children as measured by the cytokinesis-block micronucleus cytome assay. Autism Res, 8, 94-104. https://doi.org/10.1002/aur.1428
  85. Maki-Paakkanen J, Walles S, Osterman-Golkar S, et al (1991). Single-strand breaks, chromosome aberrations, sister chromatid exchanges, and micronuclei in blood lymphocytes of workers exposed to styrene during the production of reinforced plastics. Environ Mol Mutagen, 17, 27-31. https://doi.org/10.1002/em.2850170105
  86. Malla TM, Senthilkumar CS, Sharma NC, et al (2011). Chromosome instability among Bhopal gas tragedy survivors. Am Eur J Toxicol Sci, 3, 245-9.
  87. Meng Z, Zhang B (1997). Chromosomal aberrations and micronuclei in lymphocytes of workers at a phosphate fertilizer factory. Mutat Res, 393, 283-8. https://doi.org/10.1016/S1383-5718(97)00112-5
  88. Norppa H, Bonassi S, Hansteen IL, et al. (2006). Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res, 600, 37-45. https://doi.org/10.1016/j.mrfmmm.2006.05.030
  89. Pala M, Ugolini D, Ceppi M, et al (2008). Occupational exposure to formaldehyde and biological monitoring of Research Institute workers. Cancer Detection Prev, 32, 121-6. https://doi.org/10.1016/j.cdp.2008.05.003
  90. Panwar H, Mishra PK (2011). Repercussion of isocyanates exposure on different cellular proteins in human pulmonary arterial endothelial cells. Int J Res Chem Env, 1, 95-100.
  91. Panwar H, Raghuram GV, Jain D, et al (2011). Cell cycle deregulation by methyl isocyanate: implications in liver carcinogenesis. Environ Toxicol, 1-14.
  92. Pastor S, Gutierrez S, Creus A, et al (2001). Cytogenetic analysis of Greek farmers using the micronucleus assay in peripheral lymphocytes and buccal cells. Mutagenesis, 16, 539-545. https://doi.org/10.1093/mutage/16.6.539
  93. Patel BP, Trivedi PJ, Brahmbhatt MM, et al (2009) Micronuclei and chromosomal aberrations in healthy tobacco chewers and controls: A study from Gujarat, India. Arch Oncol, 17, 7-10. https://doi.org/10.2298/AOO0902007P
  94. Raghuram GV, Pathak N, Jain D, et al (2010). Molecular mechanisms of isocyanate induced oncogenic transformation in ovarian epithelial cells. Reproduct Toxicol, 30, 377-86. https://doi.org/10.1016/j.reprotox.2010.05.087
  95. Rodrigues MA, Beaton-Green LA, Kutzner BC, et al (2014). Multi-parameter dose estimations in radiation biodosimetry using the automated cytokinesis-block micronucleus assay with imaging flow cytometry. Cytometry A, 85, 883-93. https://doi.org/10.1002/cyto.a.22511
  96. Rossner P, Boffetta P, Ceppi M, et al (2005). Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer. Env Health Perspectives, 113, 517-20. https://doi.org/10.1289/ehp.6925
  97. Sarangi S, Zaidi T, Pal RK, et al (2010). Effects of exposure of parents to toxic gases in Bhopal on the offspring. Am J Ind Med, 53, 836-41.
  98. Savage AM, Pritchard JAV, Deeley TJ, et al (1980). Immunological state of patients with carcinoma of the bronchus before and after radiotherapy. Thorax, 35, 500-5. https://doi.org/10.1136/thx.35.7.500
  99. Saxena AK, Singh KP, Nagle SL, et al (1988). Effect of exposure to toxic gas on the population of Bhopal: Part IV- Immunological and chromosomal studies. Indian J Exp Biology, 26, 173-76.
  100. Scarpato R, Migliore L, Angotzi G, et al (1996). Cytogenetic monitoring of a group of Italian floriculturist: No evidence of DNA damage related to pesticide exposure. Mutat Res, 367, 73-82. https://doi.org/10.1016/0165-1218(95)00071-2
  101. Schwetz BA, Adkins BJ, Harris M. Methyl isocyanate: reproductive and developmental toxicology studies in Swiss mice. Env Health Perspectives, 72, 147-50.
  102. Sellappa S, Prathyumnan S, Joseph S, et al (2010). Genotoxic effects of textile printing dye exposed workers in India detected by micronucleus assay. Asian Pac J Cancer Prev, 11, 919-22.
  103. Sellappa S, Mani B, Keyan KS (2011a). Cytogenetic biomonitoring of road paving workers occupationally exposed to polycyclic aromatic hydrocarbons. Asian Pac J Cancer Prev, 12, 713-7.
  104. Sellappa S, Keyan KS, Prathyumnan S, et al (2011b). Biomonitoring of genotoxic effects among shielded manual metal arc welders. Asian Pac J Cancer Prev, 12, 1041-4.
  105. Senthilkumar CS (2012). Bhopal methyl isocyanate affected population and cancer susceptibility: where do we stand now? Asian Pac J Cancer Prev, 13, 5323-4. https://doi.org/10.7314/APJCP.2012.13.10.5323
  106. Senthilkumar CS, Malla TM, Sah NK, et al (2013). Methyl isocyanate exposure and atypical lymphocytes. Int J Occup Environ Med, 4, 167-8.
  107. Senthilkumar CS, Sah NK, Ganesh N (2012). Methyl isocyanate and carcinogenesis: bridgeable gaps in scientific knowledge. Asian Pac J Cancer Prev, 13, 2429-35. https://doi.org/10.7314/APJCP.2012.13.6.2429
  108. Senthilkumar CS, Tahir M, Sah NK, et al (2011). Cancer morbidity among methyl isocyanate exposed long-term survivors and their offspring: A hospital-based five year descriptive study (2006-2011) and future directions to predict cancer risk in the affected population. Asian Pac J Cancer Prev, 12, 3443-52.
  109. Shelby MD, Allen JW, Caspary WJ, et al (1987). Results of in vitro and in vivo genetic toxicity tests on methyl isocyanate. Environ Health Perspect, 72, 183-7. https://doi.org/10.1289/ehp.8772183
  110. Sitaraman S, Thirumal babu K, Badarinath ARS, et al (2014). Assessment of DNA damage using cytokinesis-block micronucleus cytome assay in lymphocytes of dilated cardiomyopathy patients. Genetics Res, 96, 1.
  111. Soares JP, Cortinhas A, Bento T, et al (2014). Aging and DNA damage in humans: A meta analysis study. Aging, 6, 432-9. https://doi.org/10.18632/aging.100667
  112. Sorsa M, Pyy L, Salomaa S, et al (1988). Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals. Mutat Res, 204, 465-79. https://doi.org/10.1016/0165-1218(88)90042-0
  113. Tates AD, Van Dam FJ, de Zwart FA, et al (1996). Biological effect monitoring in industrial workers from the Czech Republic exposed to low levels of butadiene. Toxicol, 113, 91-99. https://doi.org/10.1016/0300-483X(96)03432-4
  114. Thierens H, Vral A, Morthier R, et al (2000). Cytogenetic monitoring of hospital workers occupationally exposed to ionizing radiation using the micronucleus centromere assay. Mutagenesis, 15, 245-249. https://doi.org/10.1093/mutage/15.3.245
  115. Tice RR, Luke CA, Shelby MD (1986). Methyl isocyanate: an evaluation of in vivo cytogenetic activity. Env Mutagen, 9, 37-58.
  116. Tucker AN, Bucher JR, Germolec DR, et al (1987). Immunological studies on mice exposed subacutely to methyl isocyanate. Environ Health Perspect, 72, 139-141. https://doi.org/10.1289/ehp.8772139
  117. Varma DR, Guest I (1993). The Bhopal accident and methyl isocyanate toxicity. J Toxicol Environ Health, 40, 513-29. https://doi.org/10.1080/15287399309531816
  118. Viegas S, Ladeira C, Nunes C, et al (2010). Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyderesins production. J Occ Med Toxicol, 5, 25. https://doi.org/10.1186/1745-6673-5-25
  119. Vijayan VK (2010). Methyl isocyanate (MIC) exposure and its consequences on human health at Bhopal. Int J Environ Studies, 67, 637-53. https://doi.org/10.1080/00207233.2010.515435
  120. Wang RC, Yang L, Tang Y, et al (2013). Micronucleus expression and acute leukemia prognosis. Asian Pac J Cancer Prev, 14, 5257-61. https://doi.org/10.7314/APJCP.2013.14.9.5257
  121. Wu XY, Ni J, Xu WJ, et al (2012). Interactions between MTHFR C677T-A1298C variants and folic acid deficiency affect breast cancer risk in a Chinese population. Asian Pac J Cancer Prev, 13, 2199-206. https://doi.org/10.7314/APJCP.2012.13.5.2199
  122. Yang HY, Feng R, Liu J, et al (2014). Increased frequency of micronuclei in binucleated lymphocytes among occupationally pesticide-exposed populations: A metaanalysis. Asian Pac J Cancer Prev, 15, 6955-6960. https://doi.org/10.7314/APJCP.2014.15.16.6955
  123. Znaor A, Fucic A, Strnad M, et al (2003). Micronuclei in peripheral blood lymphocytes as a possible cancer risk biomarker: a cohort study of occupationally exposed workers in Croatia. Croat Med J, 44, 441-46.

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