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

Abstract

PurposeThe 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.MethodsWe 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.ResultsOver 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.ConclusionsBiologically significant stages of precancerous lesions were already detectable after 4 weeks of BBN exposure, considerably earlier than previously described in the literature.

Carbonic anhydrase 2 is a novel invasion‐associated factor in urinary bladder cancers

“…(15)(16)(17)(18) In the present study, we aim to establish a novel medium-term chemically-induced invasion model mimicking the invasive UC that arise from non-invasive UC and to use this model to identify invasion-associated factors. The BBN-induced rat bladder cancer model is a widely used orthotropic model of human UC with short-term treatment of BBN being capable of inducing high incidences of non-invasive UC, (18,19) and Hras128 rats exhibit high susceptibility to…”

“…(15)(16)(17)(18) In the present study, we aim to establish a novel medium-term chemically-induced invasion model mimicking the invasive UC that arise from non-invasive UC and to use this model to identify invasion-associated factors. The BBN-induced rat bladder cancer model is a widely used orthotropic model of human UC with short-term treatment of BBN being capable of inducing high incidences of non-invasive UC, (18,19) and Hras128 rats exhibit high susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis; (20,21) however, unlike other rat models, Hras128 rats treated with BBN also develop invasive UC. (20,21) In addition, it was reported that preneoplastic lesions induced by the rat urinary bladder carcinogen phenylethyl isothiocyanate (PEITC) were prone to dysplasia in rats.…”