The Changes of Histopathology, Proliferation Activity, and Nuclear DNA Content N-butyl-N-(4-hydroxybuty1) Nitrosamine(BBN) Induced Bladder Cancer in Rats

Park, Hong Seok; Cheon, Jun; Yoon, Duck Ki; Koh, Sung Kun; Kim, Han Kyeom

Abstract

To evaluate the process of tumor progression in chemical carcinogenesis of the bladder cancer. 0.05% BBN was administered to female Wistar rats for 12 weeks. The rats were divided into six groups and sacrificed every or every two weeks from the 12th to the 20th weeks. Cellular touch imprints of urinary bladder for DNA content analysis by image analyzer and mean AgNORs count per nucleus were performed immediately after sacrifice. Thereafter, the urinary bladder was embedded in paraffin for histopathological examination.On histopathological findings, simple hyperplasia was found in all cases after 12 weeks therapy of BBN. Atypical hyperplasia of the bladder, indicative of a precancerous state, was found in 88.9% of the 12 weeks group, 83.3% of the 13 weeks and in all cases after 14 weeks therapy of the BBN. Bladder cancer was found in 33.3% of the 13 weeks, 55.6% of the 14 weeks, and 100% of the above 16 weeks therapy group. The nuclear DNA content of 21 cases of atypical hyperplasia was diploid in 19 cases(91.5%) and aneuploid in 2 cases(9.5%). DNA aneuploidy was found in 18 cases(66.7%) among the 27 cases of the cancer group. Mean AgNORs count per nucleus and proliferation index by flowcytometry were higher in atypical hyperplasia and cancer group than these of simple hyperplasia and control group, but those differences according to histologic type were not statistically significant. And there was statistically significant correlation between proliferation index and mean AgNORs count per nucleus(r=0.57, p<0.05). These data suggest that the change of nuclear DNA content might occur during the early phase of the carcinogenesis in BBN-induced bladder cancer of rats.