Increased oxidative stress with gene alteration in urinary bladder urothelium after the Chernobyl accident.
We have previously shown that bladder urothelium of people living in the cesium-137 ((137)Cs)-contaminated areas of Ukraine demonstrates accumulation of stable p53 and p53 mutational inactivation, preferentially through G:C to A:T transition mutations at CpG dinucleotides, with a codon 245 hot spot. In the present study, we analyzed immuno-histochemically the relationship between oxidative stress markers and over-expression of p53 and H-ras in urinary bladder urothelium from 42 men with benign prostatic hyperplasia. Bladder mapping biopsies were obtained from 15 patients from a highly radiocontaminated area (group I), 14 patients from the less contaminated city of Kiev (group II) and 13 patients as a control group from "clean" (without radiocontamination) areas of Ukraine (group III). Irradiation cystitis with multiple foci of severe dysplasia and carcinoma in situ were observed in 15 of 15 (100%, group I) and 9 of 14 (64%, group II) cases, with 4 small transitional-cell carcinomas incidentally detected in groups I and II. Markedly elevated levels of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and 8-hydroxy-2;-deoxyguanosine (8-OHdG) were noted in these bladder urothelial lesions from groups I and II, accompanied by strong over-expression of p53 and less H-ras expression. These findings support the hypothesis that iNOS, COX-2 and 8-OHdG in bladder urothelium are induced by long-term exposure to low-dose radiation with a close relationship to p53 over-expression that could predispose to bladder carcinogenesis.
Romanenko
A
A
Department of Pathology, Institute of Urology and Nephrology, Academy of Medical Science of Ukraine, Kiev, Ukraine.
Morimura
K
K
Wanibuchi
H
H
Salim
E I
EI
Kinoshita
A
A
Kaneko
M
M
Vozianov
A
A
Fukushima
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D051546:Cyclooxygenase 2; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D011210:Power Plants; D011230:Precancerous Conditions / Q000209:etiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018788:Radioactive Hazard Release; D014455:Ukraine; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D001749:Urinary Bladder Neoplasms / Q000209:etiology
D007527:Isoenzymes; D008565:Membrane Proteins; D009569:Nitric Oxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D003849:Deoxyguanosine