Stimulation of deoxythymidine incorporation in the colon of rats treated intrarectally with bile acids and fats.

The incorporation of tritiated deoxythymidine ([3H]dThd) into colonic DNA of male Sprague-Dawley rats treated intrarectally (i.r.) with bile salts and other substances has been investigated. Instillation of sodium deoxycholate caused an increase in the incorporation of [3H]dThd which was maximal 12 h after treatment. The level of incorporation showed a steep linear dose response from 0.5 mM to 15 mM bile salt. Higher concentrations of deoxycholate up to 300 mM only slightly increased the extent of incorporation when compared to the lower concentration. Several other substances also increased the extent of [3H]dThd incorporation; these include: chenodeoxycholate, lithocholate, sodium dodecyl sulfate, dioctyl sulfosuccinate, corn oil, beef fat, and trioctanoin. Substances which had no effect on [3H]dThd incorporation include cholesterol, dehydrocholate, sodium acetate, dextrose, and mineral oil. Many of the agents which increase colonic [3H]dThd incorporation are also known to enhance colonic tumorigenesis. These findings indicate similarities between the short-term effects, in their respective target tissues, of colon tumor promoters, and classical mouse skin tumor promoters.