Chronic urinary tract infection is an important risk factor for the development of carcinoma in the human urinary bladder. To test the effect of chronic persistent inflammation on bladder carcinogenesis, we instilled heat-killed Escherichia coli (1 × 108 cells suspended in 0.5 ml of phosphate-buffered 2.1% NaCl solution) twice a week into the heterotopically transplanted rat urinary bladders in which carcinogenesis was initiated by a single dose (0.25 mg) of N-methyl-N-nitrosourea. When compared with the control animals, the rats treated with killed E. coli showed significantly enhanced bladder tumorigenesis, as reflected by an increase in the incidence of tumor (P = 0.05) and a 6- to 40-fold increase in the number of tumors per bladder (P < 0.0001). The tumors were characterized by intraepithelial clusterings of neutrophils and by chronic inflammation and marked capillary proliferation in the tumor stroma. All of these features were rare in tumors in the control groups. The accelerated cell proliferation induced by killed E. coli treatment appears to play a significant role in the enhancement of tumorigenesis.
Supported by NIH Grant CA33511.