Urinary bladder lesions induced by persistent chronic low-dose ionizing radiation.
The incidence of urinary bladder cancer in the Ukraine increased from 26.2 to 43.3 per 100,000 population between 1986 and 2001 after the Chernobyl accident. The present study was conducted to evaluate the development of radiation-dependent lesions in the urinary bladders of people living in cesium 137 ((137)Cs) radio-contaminated areas of the Ukraine. Bladder urothelial biopsies from 159 male and 5 female patients were subjected to histological examination and immunohistochemical study of p38 mitogen-activated protein kinase (MAPK), as well as the p50 and p65 subunits of nuclear factor kappa B (NF-kappa B). A pattern of chronic proliferative atypical cystitis accompanied with large areas of sclerosis of connective tissue in the lamina propria was commonly observed in all cases. Interestingly, these lesions were associated with a dramatic increase in the incidences of dysplasia/carcinoma in situ, and, moreover, small urothelial carcinomas were incidentally detected. We defined the overall condition as "Chernobyl cystitis." Greatly elevated levels of p38, p65 and p50 expression in the urothelium were evident and the patients showed increased (137)Cs in urine. The data support conclusions from our previous studies of a critical role for increased oxidative stress in generation of urinary bladder urothelial lesions in individuals chronically exposed to low-dose (137)Cs radiation. Alterations in the p38 MAPK cascade and accumulation of NF-kappa B subunits could be crucial early molecular events in the pathogenesis of Chernobyl cystitis.
Romanenko
Alina
A
Department of Pathology, Institute of Urology, Academy of Medical Sciences of Ukraine, Kiev, Ukraine. fukuchan@med.osaka-cu.ac.jp
Morimura
Keiichirou
K
Wanibuchi
Hideki
H
Wei
Min
M
Zaparin
Wadim
W
Vinnichenko
Wladimir
W
Kinoshita
Anna
A
Vozianov
Alexander
A
Fukushima
Shoji
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002588:Cesium Radioisotopes / Q000009:adverse effects / Q000652:urine; D003556:Cystitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D011210:Power Plants; D011230:Precancerous Conditions / Q000209:etiology; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D018788:Radioactive Hazard Release; D014455:Ukraine; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases
D002588:Cesium Radioisotopes; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases