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- Title
Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident.
- Authors
Romanenko, Alina; Kakehashi, Anna; Morimura, Keiichirou; Wanibuchi, Hideki; Min Wei; Vozianov, Alexander; Fukushima, Shoji
- 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-κB 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
CHORNOBYL (Ukraine); UKRAINE; BLADDER; CARCINOGENESIS; IONIZING radiation; OXIDATIVE stress; CHERNOBYL Nuclear Accident, Chornobyl, Ukraine, 1986
- Publication
Carcinogenesis, 2009, Vol 30, Issue 11, p1821
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgp193