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KMID : 1001020030010010106
Journal of Urologic Oncology
2003 Volume.1 No. 1 p.106 ~ p.111
Apotosis and Expressions of Apoptosis-related Proteins in Rat Bladder Carcinogenesis Induced by N-butyl-N-(4-hydroxybutyl) Nitrosamine
Kim Han-Gwun

Park In-Ae
Yeo Woon-Geol
Yoon Sang-Jin
Byun Seok-Soo
Lee Eun-Sik
Lee Chong-Wook
Abstract
Purpose: We investigated the role of apoptosis in rat bladder carcinogenesis induced by N-butyl-N- (4-hydroxybutyl) nitrosamine (BBN).

Materials and Methods: Rat bladder cancers were induced by 0.05% BBN in drinking water for 32 weeks. The control and experimental group were sacrificed at 8, 16, 24, 32 experimental weeks. Apoptosis was detected by routine H&E staining and apoptosis-related proteins such as p53, bcl-2, p21WAF1, mdm-2 expressions were analyzed immunohistochemically. Cellular proliferation was detected by immunohistochemical staining of proliferating cell nuclear antigen (PCNA).

Results: Histopathologic findings of rat bladder cancer induced by BBN were very similar to human bladder tumor. The number of apoptotic and proliferative cells were increased as the histopathologic stage progressed (p£¼0.01). The apoptotic cell ratio were positively correlated with proliferative cells with statistical significance (p=0.01). P53 and mdm-2 were significantly overexpressed in bladder cancer compared with control and benign lesions such as hyperplasia and papilloma (p£¼0.05). Bcl-2 was significantly overexpressed in benign and bladder cancer compared with control (p£¼0.05). The expression of p21WAF1 did not show any difference in the experimental and the control.

Conclusions: Our data suggest that the abnormality of apoptosis might be closely related to rat bladder carcinogenesis induced by BBN. The overexpression of p53, mdm-2 and bcl-2 might be associated with the abnormality of apoptosis and cellular proliferation.
KEYWORD
Bladder neoplasm, N-butyl-N-(4-hydroxybutyl) nitrosamine, Apoptosis
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