Urinary Bladder Lesions after the Chernobyl Accident: Immunohistochemical Assessment of p53, Proliferating Cell Nuclear Antigen, Cyclin D1 and p21^WAF1/Cip1

Abstract

During the 11-year period subsequent to the Chernobyl accident, the incidence of urinary bladder cancer in Ukraine has increased from 26.2 to 36.1 per 100,000 population. Cesium-137 ( 137 Cs) accounts for 80-90% of the incorporated radioactivity in this population, which has been exposed to long-term, low-dose ionizing radiation, and 80% of the more labile pool of cesium is excreted via the urine. The present study was performed to evaluate the histopathological features and the immunohistochemical status of p53, p21 WAF1/Cip1 , cyclin D1 and PCNA (proliferating cell nuclear antigen) in urinary bladder mucosa of 55 males (49-92 years old) with benign prostatic hyperplasia who underwent surgery in Kiev, Ukraine, in 1995 and 1996. Group I (28 patients) inhabiting radiocontaminated areas of the country, group II (17 patients) from Kiev city with less radiocontamination and a control group III (10 patients) living in so-called "clean" areas of Ukraine were compared. In groups I and II, an increase in multiple areas of moderate or severe dysplasia or carcinoma in situ was seen in 42 (93%) of 45 cases. In addition, two small transitional cell carcinomas were found in one patient in each of groups I and II. Nuclear accumulation of p53, PCNA, cyclin D1, and to a lesser extent p21 WAF1/Cip1 , was significantly increased in both groups I and II as compared with the control group III, indicating possible transformation events or enhancement of repair activities, that may precede the defect in the regulatory pathway itself, at least in the G1 phase of the cell cycle. Our results suggest that early malignant transformation is taking place in the bladder urothelium of people in the radiocontaminated areas of Ukraine and that this could possibly lead sometime in the future to an increased incidence of urinary bladder cancer.

Radiation sclerosing proliferative atypical nephropathy of peritumoral tissue of renal-cell carcinomas after the Chernobyl accident in Ukraine

“…Our recent studies concerning urinary bladder urothelium biopsied from 45 male patients with benign prostate hyperplasia without any bladder symptoms, living in radiocontaminated areas of Ukraine, demonstrated frequent severe urothelial dysplasia, CIS, and a single small invasive transitional cell carcinoma combined with irradiation cystitis in 42 cases (93%) [29,47]. Intratubular epithelial nuclear atypia has not been fully described in human RCC.…”

Suppressive effect of 1,4-phenylene diisothiocyanate onN-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice

“…Overexpression of cyclin D1 is implicated in the etiology of urinary bladder carcinoma. [45][46][47] It has also been reported that cyclin D1 overexpression might play a critical role in urinary tumor progression in rodent. 34-37 , 48 , 49 Some reports indicated that its overexpression could be a useful marker for estimating malignancy in the early stage of urinary carcinogenesis.…”

The INK4a/ARF locus: role in cell cycle control for renal cell epithelial tumor growth after the Chernobyl accident

“…This protein is known to accumulate in response to low doses of UV in cultured cell lines and correlates with G1 phase cell-cycle arrest [14]. Furthermore, the loss of the p16 INK4A function correlates with the loss of the UV-induced G1 arrest [20]. In the same RCCs, an increase of cyclinD1 expression occurred; although a relationship between groups was not seen.…”

“…In the same RCCs, an increase of cyclinD1 expression occurred; although a relationship between groups was not seen. However, a high level of cyclinD1 was often found in many different human tumor types-breast, urinary bladder carcinomas and squamous cell carcinomas of the head and neck [13,20].…”