N-Butyl-N-(4-Hydroxybutyl) nitrosamine에 의한 흰쥐의 방광암 발생에서의 종양원성 유전자의 역할에 관한 연구 = The Role of Oncogenes in Carcinogenesis of Urinary Bladder Cancer in Rats induced by N-Butyl-N-(4-Hydroxybutyl) nitrosamine(BBN)

다국어 초록 (Multilingual Abstract)

Bladder cancer is expected to arise through a series of genetic changes which lead to tumor progression. These changes have been directly identified as alterations of various genes usually involved in cell growth and proliferation. Fifty-two female Wistar rats were treated with BBN for 12 weeks and evaluated for the tumor progression in urinary bladder. Among 60 rats, simple hyperplasia(SH) was seen in 3, atypical hyperplasia (AH) in 19 and carcinomas (CA) in 25. Overexpression of oncoprotein of c-erb B-2, c-fos and c-H-ras and heat shock protein was evaluated by immunohistochemical staining. The DNA content was also analyzed on Feulgen stained touch imprint of bladder mucosa using CAS 200 Image Analyzer.
The obtained results were as follows :
1. DNA aneuploidy was seen in 2(9.5%) of 21 atypical hyperplasia, whereas it was found in 18 of 25(66.7%) cancer group.
2. c-H-ras oncoprotein was expressed in one of 6 normal mucosa, 2 of 3 simple hyperplasia, 15 of 19 atypical hyperpiasia, and 21 of 25 cancers.
3. The expression of c-erbB-2 oncoprotein was detected in one of 6 normal, all 3 simple hyperplasia, 18 of 19 atypical hyperplasia, and 21 of 25 cancers.
4. Expression of c-fos oncoprotein was found in all 3 simple hyperplasia, 18 of 19 atypical hyperplasia, and 24 of 25 cancers.
5. Heatshock protein 70 was not expressed in normal bladder, but expressed in 2 of 3 simple hyperplasia. 15 of 19 atypical hyperplasia, and 15 of 25 cancers.
The above data suggest that the nuclear DNA content is changed during the progression of BBN-induced changes in rat urinary bladder, and c-H-ras, c-erbB-2, c-fos and heat shock protein may play role in chemical carcinogenesis of BBN in experimental animals.