The tropic effect of intrarectal deoxycholate on rat colorectum is unaffected by oral metronidazole.

Abstract

Intrarectal administration of sodium deoxycholate (SDC) enhances experimental colorectal carcinogenesis, an effect that is partly vitiated by oral metronidazole. The effect of topical SDC with or without concurrent metronidazole on colorectal cell proliferation was explored in male Sprague-Dawley rats (n = 30) allocated to five groups. Two groups received thrice weekly intrarectal instillations of 1 ml N saline or 1 ml 0.12 M SDC. A third group received SDC plus metronidazole 22.5 mg/kg/day in the drinking water. Controls had no instillations or metronidazole alone. At time of killing (10 weeks), crypt cell production rate (CCPR) was determined by the stathmokinetic technique for four large-bowel segments. Saline had no significant effect on colorectal CCPR but SDC produced increases throughout, varying from 53% in the proximal colon to 222% in the rectum (P less than 0.01). Metronidazole did not reduce this effect, although given alone it reduced colonic CCPR by 40 to 50%. The direct tropic effect of bile acids could largely explain their cocarcinogenic properties. Since metronidazole does not prevent this increase in cell proliferation, its mildly protective role against cancer may reflect the presence of fewer anaerobes capable of degrading bile acids to carcinogenic metabolites.