Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident.
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.
Romanenko
Alina
A
Department of Pathology, Institute of Urology, Academy of Medical Sciences of Ukraine, 9a, Yu. Kotzubinsky Street, 04053 Kiev, Ukraine.
Kakehashi
Anna
A
Morimura
Keiichirou
K
Wanibuchi
Hideki
H
Wei
Min
M
Vozianov
Alexander
A
Fukushima
Shoji
S
D002453:Cell Cycle / Q000528:radiation effects; D002588:Cesium Radioisotopes; D047852:Chernobyl Nuclear Accident; D003556:Cystitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004260:DNA Repair / Q000528:radiation effects; D018450:Disease Progression; D005109:Extracellular Matrix / Q000528:radiation effects; D005260:Female; D006801:Humans; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011210:Power Plants; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011829:Radiation Dosage; D015398:Signal Transduction / Q000528:radiation effects; D013997:Time Factors; D014455:Ukraine; D001743:Urinary Bladder; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*
D002588:Cesium Radioisotopes