1. Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident.
- Author
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Romanenko A, Kakehashi A, Morimura K, Wanibuchi H, Wei M, Vozianov A, and Fukushima S
- 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
- 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.
- Published
- 2009
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