DNA replication in experimental rat bladder tumours: immunohistochemical detection of bromodeoxyuridine labelled...

With the purpose of studying DNA replication activity and location in normal and malignant tissue, bladder tumours were induced in ten rats by the intravesical installation of N-Nitroso-N-Methyl-Urea. Ten rats were installed with the NMU solvent and served as controls. The animals were injected intraperitoneally with 1 mg bromodeoxyuridine/100 g weight one hour prior to sacrifice. An indirect immunoperoxidase method using mouse monoclonal anti-bromodeoxy-uridine antibody was used on tissue sections of normal urothelium and bladder tumours to visualize labelled nuclei. Labelling indices were calculated and correlated to the grade of atypia. We found that normal urothelium had very little proliferative activity. The labelling index of tumours increased with increasing grade of atypia, being highest in invasive tumours. Only cells located to the basal cell layer were labelled in normal and grade I urothelium. In grade II and III tumours labelled cells were found in the intermediate cell layer as well as in the basal cell layer. Areas of squamous metaplasia showed high labelling indices, however the proliferative cells were restricted to the basal cell layer. The bromodeoxyuridine labelling index thus increases with increasing grade of atypia.