INVOLVEMENT OF INFLAMMATORY REACTIONS AND ELEVATED CELL-PROLIFERATIONIN THE DEVELOPMENT OF BLADDER-CANCER IN SCHISTOSOMIASIS PATIENTS

Schistosoma haematobium infection is strongly associated with urinary bladder cancer. Although numerous explanations have been proposed for this association, the nature of this relationship remains unresolved. This paper explores the hypothesis that inflammation and elevated cell proliferation play a major role in the development of bladder cancer in infected patients, possibly by increasing the level of genetic inst ability in the urothelium. The paper details in vivo and in vitro stud ies being done in our laboratories to test this hypothesis. These stud ies include population studies in which chromosomal breakage in the bl adder of infected individuals is assayed using the micronucleus (MN) t est on exfoliated urothelial cells. The approach also includes paralle l studies in Vancouver with patients with long-term catheter drainage, a population with many similarities to schistosomiasis patients. In t he in vitro studies we are co-incubating bladder cells with activated neutrophils or experimental conditions simulating inflammation. These studies show that inflammatory cells when activated can induce micronu clei in bladder cells and that this response is associated with loci o n chromosome 11, a chromosome commonly altered during bladder carcinog enesis. A final approach being used is to assay chromosomal change (MN frequencies and numerical chromosome alterations) and level of prolif eration (expression of proliferating cell nuclear antigen) in archival biopsies from schistosomiasis patients. Preliminary results show that a dysregulation of cell proliferation is occurring during cystitis in these patients. The extent to which this alteration affects the level of chromosomal breakage is yet to be determined.