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

Oncogene volume 21, pages 2398–2405 (2002)Cite this article

Abstract

Ionizing radiation is a potent lung carcinogen, but the precise molecular damage associated with it is still unknown. In this study we investigated cancer-related molecular abnormalities including K-ras (codon 12) mutation, p16INK4A promoter hypermethylation and microsatellite alterations at seven chromosomal regions in successive biopsies obtained from former Chernobyl cleanup workers in comparison with smokers and nonsmokers who have never had radiation exposure. Our results indicate that prolonged persistence of inhaled radioactive particles is associated with appearance of allelic loss at 3p12, 3p14.2 (FHIT), 3p21, 3p22-24 (hMLH1) and 9p21 (p16INK4A) in bronchial epithelium of former Chernobyl clean-up workers. The prevalence of 3p14.2 allelic loss was associated with decreased expression of the FHIT mRNA in their bronchial epithelium in comparison with control group of smokers. During several years of our monitoring samples of epithelium were collected from the same area of bronchial tree. In epithelium exposed to carcinogens (tobacco smoke and/or radioactivity) the total number of molecular abnormalities was significantly higher in dysplasia and in morphologically normal foci progressed later to dysplasia than in these samples which never showed evidence of such progression. Our findings indicate that extensive cancer-related molecular abnormalities sequentially occur in radiation damaged bronchial epithelium of former Chernobyl clean-up workers.

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Acknowledgements

We thank R Sidorov for collaboration and Drs J Schmidt, M Yakubovskaya, J Lu and P Schedin for helpful advice.

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Author notes

  1. Ekaterina Steshina

    Present address: University of Illinois at Chicago, Chicago, 60607, IL, USA

Authors and Affiliations

  1. Cancer Research Center, Moscow, Russia

    Victor Chizhikov, Alexander Gasparian, Irina Zborovskaya, Ekaterina Steshina, Guram Ungiadze & Alexander Tatosyan

  2. Institute of Pulmonology, Moscow, Russia

    Svetlana Chikina, Maria Samsonova, Andrei Chernyaev & Alexander Chuchalin

Authors
  1. Victor Chizhikov
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  2. Svetlana Chikina
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  3. Alexander Gasparian
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  6. Guram Ungiadze
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Correspondence to Alexander Tatosyan.

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Chizhikov, V., Chikina, S., Gasparian, A. et al. Molecular follow-up of preneoplastic lesions in bronchial epithelium of former Chernobyl clean-up workers. Oncogene 21, 2398–2405 (2002). https://doi.org/10.1038/sj.onc.1205310

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