Biochemical changes of intestinal epithelial cells induced by cytostatic agents in rats

In the intestinal epithelium the rapidly proliferating crypt cells, the precursors of the mature enterocytes are extremely sensitive to the effects of cytostatic agents. The symptoms of intestinal impairment: nausea, vomiting, diarrhea, ulceration, are well known both in clinical practice and in experimental chemotherapy. To obtain information about the biochemical nature of these side effects, a study was performed by investigating the influence of clinically used alkylating hexitol derivatives, dianhydrogalactitol and diacetyl-dianhydrogalactitol, on rat intestinal mucosa cells. The biochemical parameters were investigated in isolated intestinal mucosa cells. Cell proliferation was characterized by measuring the activity of thymidine kinase, while digestion was evaluated by assaying the alkaline phosphatase, sucrase and maltase activities localized in the brush border membrane of the villus cells. The dose response studies of the different enzyme activities indicated that inhibition in all cases was dose dependent. The nadir of the intestinal damage and the time of regeneration were influenced both by the dose and the dosage schedule of the drugs.