Evaluation of DNA-damaging, clastogenic, and promoting activities of metoclopramide and procainamide in rats.
The DNA-damaging and clastogenic activities of metoclopramide (MCA) and procainamide (PCA), two substituted benzamides not systematically tested for genotoxicity before clinical use, were investigated in rats given a single high oral dose (500 mg/kg) of these drugs. Neither MCA nor PCA induced DNA fragmentation in liver, kidney, gastric mucosa, spleen, and bone marrow, as detected by the alkaline elution technique. Moreover, neither drug increased the frequency of micronucleated hepatocytes and the frequency of micronucleated polychromatic erythrocytes in the bone marrow of partially hepatectomized rats. However, in rats initiated with N-nitrosodiethylamine and given water containing 0.125% MCA for 14 successive days a clear-cut and statistically significant increase in the number and size of liver gamma-glutamyltranspeptidase-positive foci and basophilic foci, which are consistent with potential promoting activity, was observed. Under the same experimental conditions the effect of PCA was markedly lower, only limited to a modest increase of the number and area of gamma-glutamyltranspeptidase-positive foci.
Mereto
E
E
Institute of Pharmacology, University of Genoa, Italy.
Robbiano
L
L
Ghia
M
M
Allavena
A
A
Martelli
A
A
Brambilla
G
G
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004247:DNA / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008787:Metoclopramide / Q000633:toxicity*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009603:Nitroso Compounds / Q000633:toxicity; D011342:Procainamide / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D009153:Mutagens; D009603:Nitroso Compounds; C008651:4-nitrosodimethylaniline; D004247:DNA; D011342:Procainamide; D008787:Metoclopramide