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Increased oxidative stress with gene alteration in urinary bladder urothelium after the Chernobyl accident
Author(s) -
Romanenko Alina,
Morimura Keiichirou,
Wanibuchi Hideki,
Salim Elsayed I.,
Kinoshita Anna,
Kaneko Masahiro,
Vozianov Alexander,
Fukushima Shoji
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000615)86:6<790::aid-ijc6>3.0.co;2-q
Subject(s) - urothelium , urinary bladder , transitional cell carcinoma , hyperplasia , oxidative stress , carcinogenesis , carcinoma in situ , dysplasia , urinary system , pathology , medicine , carcinoma , biology , urology , bladder cancer , cancer
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. Int. J. Cancer 86:790–798, 2000. © 2000 Wiley‐Liss, Inc.