N-butyl-N-(4-hydroxybutyl) nitrosamineによるラット膀胱発癌における細胞増殖の解析

Abstract

Histopathological examination, flowcytometry (FCM) study and proliferating cel1 nuclear antigen (PCNA) analysis were serially performed during the induction of carcinogenesis by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in the rat bladder, which is known to be an experimental model of human non-invasive papil1ary bladder cancer. Histological malignancy of the induced tumors was compared with the degree of cel1 proliferation by these three methods. FCM analysis revealed substantial differences of DNA change in bladder epithelial cel1s between the 4-week and 8-week treatment groups. These findings coincided with the changes observed in the histopathological examination concurrently performed. In the analysis of ploidies, tetraploid did not appear in the bladder of rats treated with BBN for 4 weeks. In PCNA analysis of epithelial cel1s in BBN-induced rat bladder carcinoma, PCNA-positive cel1sin the carcinoma increased with the severity of histopathological change. In addition, the PCNA index tended to be higher in the bladder of rats treated with BBN, which appeared to be histopathological1y normal. These findings suggest that the PCNA index serves as one useful parameter to predict the progression and proliferation of bladder carcinoma.