Enhancement of Rat Urinary Bladder Tumorigenesis by Lipopolysaccharide-induced Inflammation

Koji Kawai, Masashi Yamamoto, Shuji Kameyama, Hitoshi Kawamata, Alfred Rademaker, Ryoichi Oyasu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)5172-5175
Number of pages4
JournalCancer Research
Issue number21
StatePublished - Nov 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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