Verapamil sensitises normal and neoplastic rodent intestinal tissues to the stathmokinetic effect of vincristine in vivo

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Abstract
A morphological method has been developed allowing measurement of the effect on intestinal epithelia of vincristine. In routinely prepared tissue sections the proportion of mitotic events progressing beyond metaphase is counted by microscopy. When estimated over a range of doses of vincristine this postmetaphase index (PMI) can be used to compare the sensitivity of differing intact tissues. Intestinal tumors were induced in rats by chemical carcinogenesis. Administration of vincristine in the presence or absence of verapamil was performed in these tumor-bearing animals. Sections were prepared from colonic and small-bowel tumors and from normal mucosa. The results show that verapamil increases the sensitivity of the tissue studied to vincristine. A dose dependent effect of verapamil on vincristine sensitization was demonstrated in colonic tissues. These findings indicate a shared pharmacological property between the resistance of primary tumor tissue and the multidrug-resistance phenotype.