Aspirin inhibition of n-[4-(5-nitro-2-fury1)-2-thiazolyl]formamideinduced lesions of the urinary bladder correlated with inhibition of metabolism by bladder prostaglandin endoperoxide synthetase

Samuel M. Cohen, Shoji Fukushima, Gen’i Murasaki, Terry V. Zenser, Michael B. Mattammal, Neville S. Rapp, Bernard B. Davis

Research output: Contribution to journalArticle

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Abstract

The effects of aspirin on N44-(5-nitro-2-fury1)-2-thiazoly1]- (FANFT) -induced urinary bladder lesions, endogenous bladder prostaglandin E2 synthesis, and the metabolism of FANFT by bladder epithelial microsomes were examined. Rats were fed 0.5% aspirin and/or a diet containing 0.1% or 0.2% FANFT. Bladder lesions were observed with light and scanning electron microscopy, and the prostaglandin E2 content of rat bladder was measured by radioimmunoassay. Metabolism of FANFT was measured by decreased absorbance at 400 nm. Aspirin inhibited the appearance of hyperplastic lesions induced by feeding 0.1% or 0.2% FANFT for 6 or 12 weeks. Aspirin reduced bladder prostaglandin E2 content at 1, 2, 6, and 13 weeks compared to corresponding control values. Rat and rabbit microsomal metabolism of FANFT were dependent upon specific fatty acid substrates and prevented by specific inhibitors (including aspirin) of prostaglandin endoperoxide synthetase. Other inhibitor and substrate specificity studies suggest that FANFT was not metabolized by xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. These results suggest that the metabolism of FANFT by prostaglandin endoperoxide synthetase may be involved in the metabolic activation of FANFT necessary for the induction of bladder cancer in rats. 9, 2016.

Original languageEnglish (US)
Pages (from-to)3355-3359
Number of pages5
JournalCancer Research
Volume41
StatePublished - Sep 1 1981

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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