Mereto E, Robbiano L, Ghia M, Allavena A, Martelli A, Brambilla G
Institute of Pharmacology, University of Genoa, Italy.
Toxicol Appl Pharmacol. 1995 Apr;131(2):192-7. doi: 10.1006/taap.1995.1061.
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.
甲氧氯普胺（MCA）和普鲁卡因胺（PCA）这两种在临床使用前未系统检测遗传毒性的取代苯甲酰胺，对单次口服高剂量（500mg/kg）这些药物的大鼠进行了DNA损伤和致断裂活性研究。通过碱性洗脱技术检测，MCA和PCA均未在肝脏、肾脏、胃黏膜、脾脏和骨髓中诱导DNA片段化。此外，两种药物均未增加部分肝切除大鼠骨髓中微核化肝细胞的频率和微核化多色红细胞的频率。然而，在用N-亚硝基二乙胺启动的大鼠中，连续14天给予含0.125%MCA的水，观察到肝脏γ-谷氨酰转肽酶阳性灶和嗜碱性灶的数量和大小明显增加且具有统计学意义，这与潜在的促进活性一致。在相同实验条件下，PCA的作用明显较低，仅局限于γ-谷氨酰转肽酶阳性灶数量和面积的适度增加。
