title: DNA content analysis, expression of Ki-67 and p53 in rat urothelial lesions induced by N-butyl-N-(4-hydroxybutyl) nitrosamine and treated with mitomycin C and bacillus Calmette-Guérin.
abstract: N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urothelial carcinogenesis is a useful model for studying urothelial carcinogenesis. Here, the DNA content and the expression of Ki-67 and p53 in urothelial lesions induced by BBN and treated with mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) were investigated. Female Fisher 344 rats were distributed into five groups treated with 0.05% BBN in their drinking water for 20 weeks. Ten animals were used as negative control. Intravesical instillations were performed with MMC, BCG and physiological saline solution (PSS), once per week, for 6 weeks. The animals were sacrificed 1 week after the last intravesical instillation. DNA ploidy analysis was carried out by static cytometry. Ki-67 and p53 were analysed immunohistochemically in paraffin-embedded tissue. The incidence of lesions developed in rats with PSS was greater than in rats instilled with MMC and BCG. The incidence of aneuploidy was lower in tumours treated with MMC and BCG. Low- and high-grade papillary carcinoma treated with MMC and BCG showed a decrease in labelling index and an increase of apoptotic index. The proliferative index was correlated with the apoptotic index (r=0.438, p<0.01). Significant correlations were also found between the proliferative index and lesion, and the apoptotic index and lesion (r=0.425, p<0.01 and r=0.275, p<0.01), respectively. A significant correlation was found between ploidy and the apoptotic index (r=0.245, p<0.05). Our results provide information on the biological behaviour of chemically-induced bladder tumours treated with MMC and BCG.
authors.affiliation: Department of Veterinary Sciences, CECAV, University of Trds-os-Montes e Alto Douro, Portugal. pamo@utad.pt
authors.forename: Paula A
authors.initials: PA
authors.lastname: Oliveira
authors.forename: Carlos
authors.initials: C
authors.lastname: Palmeira
authors.forename: Aura
authors.initials: A
authors.lastname: Colaço
authors.forename: Luis F P
authors.initials: LF
authors.lastname: de la Cruz
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
mesh_terms: D000782:Aneuploidy; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001500:BCG Vaccine / Q000494:pharmacology*; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D016685:Mitomycin / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D001500:BCG Vaccine; D002273:Carcinogens; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D002085:Butylhydroxybutylnitrosamine; D016685:Mitomycin