Browse > Article
http://dx.doi.org/10.7314/APJCP.2015.16.10.4409

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.10, 2015 , pp. 4409-4419 More about this Journal
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
Methyl isocyanate exposure; long-term survivors and offspring; genotoxic effects; Bhopal; India;
Citations & Related Records
Times Cited By KSCI : 11  (Citation Analysis)
연도 인용수 순위
1 Hogstedt B (1984). Micronuclei in lymphocytes with preserved cytoplasm: a method for assessment of cytogenetic damage in man. Mutat Res, 130, 63-72.   DOI
2 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.
3 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.   DOI
4 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)
5 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
6 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
7 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.   DOI
8 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.   DOI
9 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.   DOI
10 Joksic G, Vidakovic A, Spasojevic-Tisma V (1997). Cytogenetic monitoring of pesticide sprayers. Environ Mol Mutagen, 75, 113-8.
11 Kapoor R (1991). Fetal loss and contraceptive acceptance among the Bhopal gas victims. Soc Biol, 38, 242-8.
12 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.   DOI
13 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.   DOI
14 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.   DOI
15 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.
16 Luster MI (1986). Immunotoxicity studies on mice exposed to methyl isocyanate. Toxicol Appl Pharmacology, 86, 140-4.   DOI
17 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.   DOI
18 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.   DOI
19 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.   DOI
20 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.   DOI
21 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.   DOI
22 Malla TM, Senthilkumar CS, Sharma NC, et al (2011). Chromosome instability among Bhopal gas tragedy survivors. Am Eur J Toxicol Sci, 3, 245-9.
23 Meng Z, Zhang B (1997). Chromosomal aberrations and micronuclei in lymphocytes of workers at a phosphate fertilizer factory. Mutat Res, 393, 283-8.   DOI
24 Norppa H, Bonassi S, Hansteen IL, et al. (2006). Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res, 600, 37-45.   DOI
25 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.   DOI
26 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.   DOI
27 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.
28 Panwar H, Raghuram GV, Jain D, et al (2011). Cell cycle deregulation by methyl isocyanate: implications in liver carcinogenesis. Environ Toxicol, 1-14.
29 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.   DOI
30 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.   DOI
31 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.   DOI
32 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.   DOI
33 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.
34 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.   DOI
35 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.
36 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.
37 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.   DOI
38 Schwetz BA, Adkins BJ, Harris M. Methyl isocyanate: reproductive and developmental toxicology studies in Swiss mice. Env Health Perspectives, 72, 147-50.
39 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.
40 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.
41 Senthilkumar CS (2012). Bhopal methyl isocyanate affected population and cancer susceptibility: where do we stand now? Asian Pac J Cancer Prev, 13, 5323-4.   DOI
42 Senthilkumar CS, Malla TM, Sah NK, et al (2013). Methyl isocyanate exposure and atypical lymphocytes. Int J Occup Environ Med, 4, 167-8.
43 Senthilkumar CS, Sah NK, Ganesh N (2012). Methyl isocyanate and carcinogenesis: bridgeable gaps in scientific knowledge. Asian Pac J Cancer Prev, 13, 2429-35.   DOI
44 Soares JP, Cortinhas A, Bento T, et al (2014). Aging and DNA damage in humans: A meta analysis study. Aging, 6, 432-9.   DOI
45 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.
46 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.   DOI
47 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.
48 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.   DOI
49 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.   DOI
50 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.   DOI
51 Tice RR, Luke CA, Shelby MD (1986). Methyl isocyanate: an evaluation of in vivo cytogenetic activity. Env Mutagen, 9, 37-58.
52 Tucker AN, Bucher JR, Germolec DR, et al (1987). Immunological studies on mice exposed subacutely to methyl isocyanate. Environ Health Perspect, 72, 139-141.   DOI
53 Wang RC, Yang L, Tang Y, et al (2013). Micronucleus expression and acute leukemia prognosis. Asian Pac J Cancer Prev, 14, 5257-61.   DOI
54 Varma DR, Guest I (1993). The Bhopal accident and methyl isocyanate toxicity. J Toxicol Environ Health, 40, 513-29.   DOI
55 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.   DOI
56 Vijayan VK (2010). Methyl isocyanate (MIC) exposure and its consequences on human health at Bhopal. Int J Environ Studies, 67, 637-53.   DOI
57 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.   DOI   ScienceOn
58 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.   DOI
59 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.
60 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.   DOI   ScienceOn
61 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)
62 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.   DOI
63 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.
64 Anwar WA, Gabal MS (1991). Cytogenetic study in workers occupationally exposed to mercury fulminate. Mutagenesis, 6, 189-92.   DOI
65 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.   DOI
66 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.   DOI
67 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.   DOI
68 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.   DOI
69 Bolognesi C, Creus A, Wegman PO, et al (2011). Micronuclei and pesticide exposure. Mutagenesis, 26, 19-26.   DOI
70 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.
71 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.   DOI
72 Bolognesi C, Parrini M, Bonassi S, et al (1993). Cytogenetic analysis of a human population occupationally exposed to pesticides. Mutat Res, 285, 239-49.   DOI
73 Bolognesi C, Perrone E, Landini E (2002). Micronucleus monitoring of a floriculturist population from Western Liguria, Italy. Mutagenesis, 17, 391-7.   DOI
74 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.   DOI
75 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.
76 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.   DOI
77 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.   DOI
78 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.   DOI
79 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.
80 Bucher JR (1987). Methyl isocyanate: A review of health effects research since Bhopal. Fund Appl Toxicol, 9, 367-79.   DOI
81 Calvert GM, Talaska G, Mueller CA, et al (1998). Genotoxicity in workers exposed to methyl bromide. Mutat Res, 417, 115-28.   DOI
82 Carter SB (1967). Effects of cytochalasins on mammalian cells. Nature, 213, 261-4.   DOI
83 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.
84 Costa C, Teixeira JP, Silva S, et al (2006). Cytogenetic and molecular biomonitoring of a Portuguese population exposed to pesticides. Mutagenesis, 21, 343-50.   DOI
85 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.   DOI
86 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.   DOI
87 Das RK, Das BC (1992). Genotoxicity of gudakhu a tobacco preparation II. In habitual users. Food Chem Toxicol, 12, 1045-52.
88 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.
89 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.   DOI
90 Declaration of Helsinki (DoH) (2000). World Medical Association. Available from URL: http://www.wma.net/[accessed on June 7, 2007 and February 18, 2010].
91 Dhara VR, Dhara R (2002). The Union Carbide disaster in Bhopal: a review of health effects. Arch Environ Health, 57, 391-404.   DOI
92 Dhara VR, Kriebel D (1993). The Bhopal gas disaster: It's not too late for sound epidemiology. Arch Environ Health, 48, 436-7.   DOI
93 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.   DOI
94 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.   DOI
95 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.   DOI
96 Eastmond DA, Tucker JD (1989). Identification of aneuploidyinducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody. Environ Mol Mutagen, 13, 34-43.   DOI
97 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.   DOI
98 El-Zein R, Vral A, Etzel CJ (2011). Cytokinesis-blocked micronucleus assay and cancer risk assessment. Mutagenesis, 26, 101-6.   DOI
99 Ennever FK, Rosenkranz HS (1987). Evaluating the potential for genotoxic carcinogenicity of methyl isocyanate. Toxicol Appl Pharmacol, 91, 502-5.   DOI
100 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.   DOI   ScienceOn
101 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.   DOI
102 Fenech M (2000). The in vitro micronucleus technique. Mutat Res, 455, 81-95.   DOI
103 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.   DOI
104 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.   DOI   ScienceOn
105 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.   DOI   ScienceOn
106 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.   DOI
107 Fenech M, Morley AA (1985a). Measurement of micronuclei in lymphocytes. Mutat Res, 147, 29-36.   DOI
108 Fenech M, Morley AA (1985b). The effect of donor age on spontaneous and induced micronuclei. Mutat Res, 148, 99-105.   DOI
109 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.   DOI
110 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.   DOI
111 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.   DOI
112 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.   DOI
113 Ganesh N, Sanyal B, Panday RK, et al (2005). Cancer patterns among MIC gas survivors and their offspring. Health administrator, 17, 50-58.
114 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.
115 Goswami HK (1986). Cytogenetic effects of methyl isocyanate exposure in Bhopal. Hum Genet, 74, 42-45.
116 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.   DOI
117 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.   DOI
118 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.   DOI
119 Goswami HK, Chandolkar M, Bhattacharya K, et al (1990). Search for chromosomal variations among gas exposed persons in Bhopal. Hum Genet, 84, 172-76.
120 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.
121 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.
122 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.   DOI
123 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.   DOI