title: DNA cytophotometric and histological analysis of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced precancerous lesions of the bladder urothelium.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Pathology, Hirschlandstraße 97, 73730, Esslingen, Germany. hhdahm@espath.de.
authors.forename: Hans Helmut
authors.initials: HH
authors.lastname: Dahm
authors.affiliation: Gynecological Practice, Tiberstraße 7, 48249, Dülmen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: von der Haar
authors.affiliation: Clinic and Policlinic of Urology, Hufelandstraße 55, 45147, Essen, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Rübben
mesh_terms: D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000032:analysis*; D005260:Female; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology
chemical_list: D002273:Carcinogens; D002085:Butylhydroxybutylnitrosamine; D004247:DNA
keywords: Carcinogenesis; DNA cytophotometry; N-butyl-N-(4-hydroxybutyl)nitrosamine; Urothelium