DNA cytophotometric and histological analysis of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced precancerous lesions of the bladder urothelium

PURPOSE - The morphology of experimentally induced urinary bladder precancerous lesions has been differentially interpreted in the literature. Here, we aimed to describe the development of precancerous lesions of the urothelium histologically and by DNA cytophotometric analysis.

METHODS - We induced precancerous lesions of the urothelium in 60 Wistar rats with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) solution as drinking water. After exposure for 2-20 weeks, each animal received tap water for 2 weeks. Subsequently, six animals were killed every 2 weeks, and urothelia of three urinary bladders per time point were examined by DNA cytophotometry of smear preparations. An additional three urinary bladders were processed for histological analysis.

RESULTS - Over 20 weeks, BBN exposure led to a significant difference between the control group and most of the BBN-exposed 2-week groups and to differences between most of these time point groups. After week 4, this difference included a higher proportion of cells with increased nuclear DNA content. At the end of the experiment, DNA cytophotometric values of the urothelium in experimental rats corresponded to those of poorly differentiated urothelial carcinomas.

CONCLUSIONS - Biologically significant stages of precancerous lesions were already detectable after 4 weeks of BBN exposure, considerably earlier than previously described in the literature.

Journal of cancer research and clinical oncology. 2016 Mar 31 [Epub ahead of print]

Hans Helmut Dahm, Claudia von der Haar, Herbert Rübben

Institute of Pathology, Hirschlandstraße 97, 73730, Esslingen, Germany. Gynecological Practice, Tiberstraße 7, 48249, Dülmen, Germany., Clinic and Policlinic of Urology, Hufelandstraße 55, 45147, Essen, Germany.