Effect of Indomethacin on Intestinal Tumors Induced in Rats by the Acetate Derivative of Dimethylnitrosamine

Abstract

Over the course of 20 weeks, Sprague-Dawley rats developed intestinal tumors in response to an intraperitoneal injection of the acetate derivative of dimethylnitrosamine. The same agent did not induce tumors in Lobund-Wistar rats. The number of tumors was significantly smaller in rats given drinking water containing indomethacin (beginning 14 days after the injections) than in control rats given drug-free water.

Reduction of acetoxymethyl-methylnitrosamine-induced large bowel cancer in rats by indomethacin.

“…The result is in agreement with a study by Pollard and Luckert (1981), in which indomethacin given after single intraperitoneal injection of a large dose of AMMN prevented the tumor development in the large bowel as well as in the small bowel. It has been also demonstrated that the drug inhibited the promotion and/or progression of large bowel tumor development induced by intrarectal instillation of N-methylnitrsourea (Narisawa et al 1981;.…”

Inhibition of mammary carcinogenesis by flurbiprofen, a non-steroidal antiinflammatory agent

“…As indicated in Table I The inhibition of mammary carcinogenesis by inhibitors of arachidonic acid metabolism such as flurbiprofen is consistent with studies performed in other experimental tumour models, notably mouse skin -and rat colon (Verma et al, 1980;Pollard & Luckert, 1981;Narisawa et al, 1981). The mechanism(s) by which these agents inhibit cancer induction are unknown, although influences on cell kinetics (Bayer et al, 1979;Boynton & Whitfield, 1980), mammary gland differentiation (MiyamotoTiaven et al, 1981;McCormick & Moon, 1983b), and immune function (Droller et al, 1978;Glaser, 1980) may be involved.…”

Role of eicosanoids on intestinal epithelial homeostasis

“…Early in the 11 neoplastic process, eicosanoids could be powerful tumor promoters, producing an attractive environment for tumor growth and promoting angiogenesis. Thus, studies in the early 1980s indicated that non-steroidal anti-inflammatory drugs (NSAIDs) were chemopreventive in animal models of colon cancer [38]. In 1991, Thun et al [39] reported that aspirin use reduce the relative risk of colon cancer and colon cancer mortality among 600,000 individuals, whereas acetaminophen, which does not affect COX activity, did not provide as protective an effect.…”