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Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident.
- Source :
-
Carcinogenesis [Carcinogenesis] 2009 Nov; Vol. 30 (11), pp. 1821-31. Date of Electronic Publication: 2009 Jul 30. - Publication Year :
- 2009
-
Abstract
- Urinary bladder urothelium as well as cells in the microenvironment of lamina propria (endothelial elements, fibroblasts and lymphocytes) demonstrate a number of responses to chronic persistent long-term, low-dose ionizing radiation (IR). Thus, oxidative stress occurs, accompanied by up-regulation of at least two signaling pathways (p38 mitogen-activated protein kinase and nuclear factor-kappaB cascades) and activation of growth factor receptors, in the bladder urothelium of people living in Cesium 137-contaminated areas of Ukraine, resulting in chronic inflammation and the development of proliferative atypical cystitis, so-called Chernobyl cystitis, which is considered a possible pre-neoplastic condition in humans. Furthermore, significant alterations in regulation of cell cycle transitions are associated with increased cell proliferation, along with up-regulated ubiquitination and sumoylation processes as well as inefficient DNA repair (base and nucleotide excision repair pathways) in the affected urothelium. The microenvironmental changes induced by chronic long-term, low-dose IR also appear to promote angiogenesis and remodeling of the extracellular matrix that could facilitate invasion as well as progression of pre-existing initiated cells to malignancy. Based on the available findings, new strategies have been developed for predicting and treatment of Chernobyl cystitis-a first step in urinary bladder carcinogenesis in humans.
- Subjects :
- Cell Cycle radiation effects
Cesium Radioisotopes
Cystitis metabolism
Cystitis pathology
DNA Repair radiation effects
Disease Progression
Extracellular Matrix radiation effects
Female
Humans
Male
Neoplasms, Radiation-Induced pathology
Neovascularization, Pathologic metabolism
Neovascularization, Pathologic pathology
Precancerous Conditions pathology
Radiation Dosage
Signal Transduction radiation effects
Time Factors
Ukraine
Urinary Bladder
Urinary Bladder Neoplasms metabolism
Urinary Bladder Neoplasms pathology
Urothelium blood supply
Urothelium metabolism
Urothelium pathology
Chernobyl Nuclear Accident
Cystitis etiology
Neoplasms, Radiation-Induced metabolism
Power Plants
Precancerous Conditions metabolism
Urinary Bladder Neoplasms etiology
Urothelium radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 30
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 19643821
- Full Text :
- https://doi.org/10.1093/carcin/bgp193