ASPIRIN, BUT NOT SODIUM-SALICYLATE, INDOMETHACIN, OR NABUMETONE, REVERSIBLY SUPPRESSES 1,2-DIMETHYLHYDRAZINE-INDUCED COLONIC ABERRANT CRYPTFOCI IN RATS

The aim of this study was to determine if selective inhibition of cycl ooxygenase isozymes affects the initiation of carcinogen-induced colon cancer using aberrant crypt foci (ACF) as a surrogate biomarker, Male Sprague-Dawley rats (18 per group) were given single subcutaneous inj ections of saline (4 ml/kg), aspirin (50 mg/kg body wt) sodium salicyl ate (50 mg/kg), indomethacin (4 mg/kg), nabumetone (100 mg/kg), or 16, 16-dimethyl-prostaglandin E-2 (50 mg/kg) for three days. On day 4, 12 rats per group were given a subcutaneous injection of 1,2-dimethylhydr azine (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 lat er. 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 b etween groups, ACF from all treatment groups increased in size at simi lar rates at both time points, Thus, only aspirin demonstrated a signi ficant, although reversible, suppression of carcinogen-induced ACF. Po ssible mechanisms of action and the clinical implications of aspirin c hemoprevention are discussed.