Molecular follow-up of preneoplastic lesions in bronchial epithelium of former Chernobyl clean-up workers

Chizhikov, Victor V.; Чикина, С. Ю.; Gasparian, Alexander V.; Zborovskaya, I. B.; Steshina, Ekaterina Y.; Унгиадзе, Г. В.; Самсонова, М. В.; Chernyaev, Andrei; Chuchalin, Alexander; Tatosyan, A. G.

doi:10.1038/sj.onc.1205310

Cited by 19 publications

(14 citation statements)

References 25 publications

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“…In this study, malignant mesothelioma cases associated with occupational asbestos exposure showed frequent reduction of Fhit protein expression. These observations further support previous suggestions that the FHIT gene alterations may be involved in the development of neoplasms associated with environmental carcinogen exposure [2,6,22,26]. In conclusion, our present data show that absent or markedly reduced Fhit expression was frequent in MM.…”

Section: Discussionsupporting

confidence: 94%

Reduced Fhit protein expression in human malignant mesothelioma

et al. 2004

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Human malignant mesothelioma (MM) is an aggressive neoplasm related to occupational exposure to asbestos and characterised by a long latency time. Multiple chromosomal deletions and DNA losses have been revealed in MM by studies performed with karyotypic, comparative genomic hybridisation and loss of heterozygosity (LOH) analyses. Among frequently deleted chromosomal sites, LOH at chromosome 3p has been detected in MM, suggesting the presence of one or several tumour suppressor genes that have an important role in development of the disease. The FHIT (fragile histidine triad) tumour suppressor gene, located at 3p14.2, has been proposed to be a target to major human lung carcinogens, such as tobacco smoke and asbestos. Although many studies have indicated decreased Fhit protein expression in a variety of malignancies, there is no report of FHIT gene aberrations or Fhit protein abnormalities in MM. We examined expression of the Fhit protein and LOH at the FHIT gene in malignant mesothelioma. Altogether, 13 paraffin embedded MM tumours were analysed for Fhit protein expression, and 21 fresh tumours and 10 cell cultures for LOH at the FHIT gene with two intragenic microsatellite markers. All tumours showed less intense immunostaining than normal bronchial epithelium or mesothelium. Fhit expression was absent or reduced in 54% (7 of 13) of the tumours, with the weakest staining observed in poorly differentiated areas. Allele loss was seen in 3 of 10 (30%) of the MM cell lines, but only in 1 of the 21 fresh tumours studied, suggesting concealment of LOH by normal cells present in MM tumours. In conclusion, our present data indicate a frequent decrease of Fhit protein expression, thus supporting the significance of FHIT inactivation in development of MM.

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Section: Discussionsupporting

confidence: 94%

Reduced Fhit protein expression in human malignant mesothelioma

et al. 2004

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“…However, one of the main problems in studying LOH in mitosis is the very low frequency of spontaneous events that can be analyzed in vitro. Nevertheless, LOH may be randomly induced by a variety of physical and chemical agents (Chizhikov et al 2002;Pan et al 2005;Daigaku et al 2006). LOH may also be induced by transposition of DNA-RNA molecules, such as the Moloney murine leukemia virus (Lander and Fan 1997), with considerably higher frequency.…”

Section: Introductionmentioning

confidence: 98%

DNA bridging of yeast chromosomes VIII leads to near-reciprocal translocation and loss of heterozygosity with minor cellular defects

Tosato

Nicolini²,

Bruschi

2008

Chromosoma

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Loss of heterozygosity (LOH) of tumor suppressor genes in somatic cells is a major process leading to several types of cancer; however, its underlying molecular mechanism is still poorly understood. In the present work, we demonstrate that a linear DNA molecule bridging two homologous chromosomes in diploid yeast cells via homologous recombination produce LOH-generating regions of hemizygosity by deletion. The result is a near-reciprocal translocation mutant that is characterized by slight cell cycle defects and increased expression of the multidrug-resistant gene VMR1. When the distance between target regions is approximately 40 kb, the specificity of gene targeting becomes less stringent and an ensemble of gross chromosomal rearrangements arises. These heterogeneous genomic events, together with the low frequency of specific translocation, confirm that several pathways contribute to the healing of a broken chromosome and suggest that uncontrolled recombination between parental homologs is actively avoided by the cell. Moreover, this work demonstrates that the common laboratory practice of making targeted gene deletions may result in a low, but not negligible, frequency of LOH due to the recombination events triggered between homologous chromosomes in mitosis.

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“…When inhaled, the radionuclides can affect the respiratory system even without the presence of the other coal ash components. Thus, the airborne particles containing radioactive elements inhaled by cleanup workers of the nuclear accident at the Chernobyl nuclear power plant caused bronchial mucosa lesions, in some cases preneoplastic, with an increased susceptibility to the invasion of microorganisms in bronchial mucosa (60,61). Consequently, the combined radioactivity of coal ash at the TVA spill, together with other enriched trace metals such as Ni, Pb, and As, may increase the overall health impact in exposed populations, depending on duration of exposure, and particularly for susceptible groups of the population.…”

Section: Ra/ 226mentioning

confidence: 99%

Survey of the Potential Environmental and Health Impacts in the Immediate Aftermath of the Coal Ash Spill in Kingston, Tennessee

Ruhl

Vengosh

Dwyer

et al. 2009

Environ. Sci. Technol.

162

134

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An investigation of the potential environmental and health impacts in the immediate aftermath of one of the largest coal ash spills in U.S. history at the Tennessee Valley Authority (TVA) Kingston coal-burning power plant has revealed three major findings. First, the surface release of coal ash with high levels of toxic elements (As = 75 mg/kg; Hg = 150 μg/kg) and radioactivity (226Ra + 228Ra = 8 pCi/g) to the environment has the potential to generate resuspended ambient fine particles (<10 μm) containing these toxics into the atmosphere that may pose a health risk to local communities. Second, leaching of contaminants from the coal ash caused contamination of surface waters in areas of restricted water exchange, but only trace levels were found in the downstream Emory and Clinch Rivers due to river dilution. Third, the accumulation of Hg- and As-rich coal ash in river sediments has the potential to have an impact on the ecological system in the downstream rivers by fish poisoning and methylmercury formation in anaerobic river sediments.

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Molecular follow-up of preneoplastic lesions in bronchial epithelium of former Chernobyl clean-up workers

Cited by 19 publications

References 25 publications

Reduced Fhit protein expression in human malignant mesothelioma

Reduced Fhit protein expression in human malignant mesothelioma

DNA bridging of yeast chromosomes VIII leads to near-reciprocal translocation and loss of heterozygosity with minor cellular defects

Survey of the Potential Environmental and Health Impacts in the Immediate Aftermath of the Coal Ash Spill in Kingston, Tennessee

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