title: Cell proliferation and DNA content in rat urothelial lesions after repeat intravesical instillations of mitomycin C and bacillus Calmette-Guérin.
abstract: OBJECTIVE
  To study cell proliferation and DNA content in urothelial lesions identified after repeated intravesical instillations of mitomycin C (MMC) and bacillus Calmette-Guérin (BCG) in normal rat urothelium.
  
  
  METHODS
  A total of 45 rats were divided into nine equal groups: those intravesically instilled with MMC; those receiving BCG intravesically, and a control group intravesically instilled with a physiological solution of sodium chloride (SF). Animals were killed 1, 4 or 8 weeks after the last intravesical instillation. An immunohistochemical streptavidin-biotin-peroxidase technique was performed to investigate Ki-67 expression and the DNA ploidy status was measured using static cytometry.
  
  
  RESULTS
  In urothelium exposed to MMC lesions such as simple hyperplasia, dysplasia, carcinoma in situ(CIS), and squamous cell metaplasia were identified. The proliferation index presented values of 11.73, 22.43 and 31.46% in hyperplasias, dysplasias, and CIS, respectively (p < 0.05). The frequency of abnormal DNA content amongst those animals exhibiting simple hyperplasias 25% were aneuploid, in the dysplasia 85.2% were aneuploid (p = 0.041). CIS were all multiploid, and squamous cell metaplasias were all diploid. Animals treated with BCG and SF presented no urothelial lesions and a diploid DNA content.
  
  
  CONCLUSIONS
  The aneuploid and multiploid DNA content and proliferation index observed in urothelial lesions identified after repeated intravesical instillations of MMC reflect a high degree of genomic instability in such lesions which in itself may lead to rapid regeneration of new phenotypes.
authors.affiliation: Department of Veterinary Sciences, CECAV, University of Trás-os-Montes e Alto Douro, Vila Real, Portugal. pamo@utad.pt
authors.forename: P
authors.initials: P
authors.lastname: Oliveira
authors.forename: C
authors.initials: C
authors.lastname: Palmeira
authors.forename: A
authors.initials: A
authors.lastname: Colaço
authors.forename: L F
authors.initials: LF
authors.lastname: De la Cruz P
authors.forename: C
authors.initials: C
authors.lastname: Lopes
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage*; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism*; D005260:Female; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D016685:Mitomycin / Q000008:administration & dosage*; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D012965:Sodium Chloride / Q000494:pharmacology; D016896:Treatment Outcome; D001745:Urinary Bladder Diseases / Q000188:drug therapy*; D019459:Urothelium / Q000473:pathology*
chemical_list: D001500:BCG Vaccine; D019394:Ki-67 Antigen; D012965:Sodium Chloride; D016685:Mitomycin; D004247:DNA