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Enhancement of Rat Urinary Bladder Tumorigenesis by Lipopolysaccharide-induced Inflammation¹

Department of Pathology [K. K., M. Y., S. K., H. K., R. O.], Northwestern University Medical School, and Northwestern University Cancer Center Biometry Section [A. R.], Chicago, Illinois 60611-3008

Chronic inflammation of the urinary tract is a significant risk factor for the development of urinary bladder cancer in humans. We previously demonstrated that weekly treatment with killed Escherichia coli enhanced rat urinary bladder tumorigenesis initiated by the carcinogen N-methyl-N-nitrosourea. We conducted the present study to determine whether lipopolysaccharide (LPS), a major cell wall component of E. coli, had a tumor-enhancing effect. LPS was instilled twice a week at three doses (100, 1.0, and 0.01 µg/ml) into heterotopically transplanted rat urinary bladders which were treated with a single low dose (0.25 mg) of N-methyl-N-nitrosourea or vehicle. Rats treated with 100 µg/ml of LPS showed a significant increase in the incidence and number of tumors in the bladders pretreated with N-methyl-N-nitrosourea. Treatment with LPS alone did not induce tumors. The enhancing effects were associated with a marked increase in the numbers of polymorphonuclear leukocytes and an increase in the H₂O₂ concentration in the bladder lumen. Oxidative stress by reactive oxygen intermediates and a proliferative response of the carcinogen-exposed urothelium to the inflammatory stimulation appeared to play a significant role in tumor enhancement by LPS.

¹ Supported by NIH Grant CA33511.

² To whom requests for reprints should be addressed, at Department of Pathology, Northwestern University Medical School, Ward Memorial Building, 303 East Chicago Avenue, Chicago, IL 60611-3008.

Received 6/ 1/93. Accepted 8/26/93.

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