Inhibition by verapamil of cholecystokinin-enhancement of pancreatic carcinogenesis induced by azaserine in Wistar rats

The effect of a calcium channel blocker, verapamil, on cholecystokinin (CCK)-enhancement of pancreatic carcinogenesis induced by azaserine was investigated in Wistar rats. During and after 25 weekly injections of azaserine, each rat received alternate-day injections of CCK-octapeptide (CCK-8) and/or verapamil. Carcinogen-induced pancreatic lesions staining for μ class glutathione 5-transferase (GST-μ) were examined histochemically at week 62. Prolonged administration of CCK-8 significantly increased the number and area as a percentage of parenchyma of GST-μ-positive lesions. Concomitant administration of verapamil significantly attenuated the enhancing effect of CCK-8. These findings indicate that calcium may play an important role in CCK-enhancement of pancreatic carcinogenesis.