EVALUATION OF DNA-DAMAGING, CLASTOGENIC, AND PROMOTING ACTIVITIES OF METOCLOPRAMIDE AND PROCAINAMIDE IN RATS

The DNA-damaging and clastogenic activities of metoclopramide (MCA) an d procainamide (PCA), two substituted benzamides not systematically te sted for genotoxicity before clinical use, were investigated in rats g iven a single high oral dose (500 mg/kg) of these drugs. Neither MCA n or PCA induced DNA fragmentation in liver, kidney, gastric mucosa, spl een, and bone marrow, as detected by the alkaline elution technique. M oreover, neither drug increased the frequency of micronucleated hepato cytes and the frequency of micronucleated polychromatic erythrocytes i n the bone marrow of partially hepatectomized rats. However, in rats i nitiated with N-nitrosodiethylamine and given water containing 0.125% MCA for 14 successive days a clear-cut and statistically significant i ncrease in the number and size of liver gamma-glutamyltranspeptidase-p ositive foci and basophilic foci, which are consistent with potential promoting activity, was observed. Under the same experimental conditio ns the effect of PCA was markedly lower, only limited to a modest incr ease of the number and area of gamma-glutamyltranspeptidase-positive f oci. (C) 1995 Academic Press, Inc.