Aspirin, but not sodium salicylate, indomethacin, or nabumetone, reversibly suppresses 1,2-dimethylhydrazine-induced colonic aberrant crypt foci in rats

Christopher J. Barnes, Elaine Hardman, Ivan L. Cameron, Makau Lee

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The aim of this study was to determine if selective inhibition of cyclooxygenase isozymes affects the initiation of carcinogen-induced colon cancer using aberrant crypt loci (ACF) as a surrogate biomarker. Male Sprague-Dawley rats (18 per group) were given single subcutaneous injections of saline (4 ml/kg), aspirin (50) mg/kg body wt) sodium salicylate (50) mg/kg), indomethacin (4 mg/kg), nabumetone (100) mg/kg), or 16,16-dimethyl- prostaglandin E2 (50 mg/kg) for three days. On day 4, 12 rats per group were given a subcutaneous injection of 1,2-dimethylhydrazine (12 mg base/kg body wt) and six rats per group received vehicle alone (4 ml/kg) every week for eight weeks, after which drug treatment ceased. (Control and six carcinogen- treated rats per group were killed at this time and the remaining six rats per group killed 22 weeks later. Colons were scored for ACF number and size. Only aspirin caused a significant reduction in total ACF and ACF formation at the early time point, but at the later time, there were no significant differences between groups. ACF from all treatment groups increased in size at similar rates at both time points. Thus, only aspirin demonstrated a significant, although reversible, suppression of carcinogen-induced ACF. Possible mechanisms of action and the clinical implications of aspirin chemoprevention are discussed.

Original languageEnglish (US)
Pages (from-to)920-926
Number of pages7
JournalDigestive Diseases and Sciences
Volume42
Issue number5
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • aberrant crypt foci
  • aspirin
  • carcinogenesis
  • colon
  • indomethacin
  • nabumetone
  • prostaglandin E
  • rat
  • sodium salicylate

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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