CELL-PROLIFERATION INDUCED BY LAXATIVES AND RELATED-COMPOUNDS IN THE RAT INTESTINE

Induction of cell proliferation by laxatives and related compounds in rat intestines was analysed by BrdU-labelling and compared with histop athological changes in the mucosa and findings for feces. Male F344 ra ts were fed a diet containing danthron, sennosid A, bisacodyl, 1-hydro xyanthraquinone (1-HAQ), magnesium sulfate (MgSO4), dextran sulfate so dium (DSS); pectin, carboxymethylcellulose sodium (CMC-Na) or sodium c hloride (NaCl) for 7 days. The stimulant laxatives, danthron, sennosid A and bisacodyl, significantly induced cell proliferation in almost t he entire intestinal epithelia in a clear dose-dependent manner. DSS a lso induced cell proliferation in some portions at high doses. Increas e in BrdU-labelling indices was correlated well with the severity of i nflammatory changes in the intestinal mucosa as well as with purging e ffects of stimulant laxatives and DSS. In contrast, the bulk-forming l axative CMC-Na did not consistently enhance cell proliferation nor cau se apparent cytotoxicity in the intestine despite exerting remarkable purging effects. 1-HAQ and MgSO, slightly induced cell proliferation i n the cecum and the colorectum, although there was little or no intest inal cytotoxicity. Pectin and NaCl did not influence cell kinetics of the epithelia, nor cause any inflammatory changes in the mucosa. Our r esults thus indicate that diarrhea caused by laxatives is not necessar ily correlated with induction of cell proliferation, as in the intesti nal mucosa, and that inflammatory changes followed by regenerative pro cess could be responsible for enhancing cell kinetics. Although the pr ecise significance of cell proliferation in carcinogenesis remains unc lear, it is crucial for setting doses of carcinogenicity testings that charges in cell kinetics caused by chemicals be taken into account.