Cholecystokinin inhibits DNA alkylation induced by N-nitrosobis (2-oxopropyl)amine (BOP) in hamster pancreas

Cholecystokinin (CCK) inhibits pancreatic cancer but not hepatic tumor induction by N-nitrosobis (2-oxopropyl) amine (BOP) in hamsters when administered with or shortly before BOP. In this study, we evaluated the capability of sulfated CCK-8 to inhibit DNA alkylation in the hamster pancreas. We examined the pattern of O⁶-methylguanine (G⁶-Me) and N⁷-methylguanine (G⁷-Me) in pancreatic ductal, acinar and liver tissues from Syrian hamsters treated with a single dose of BOP (20 mg/kg s.c.) and with five s.c. injections of CCK-8 (200 pM/kg, 30 min apart). The first CCK injection was given either 90 min before, or together, or 3 h after POP administration. The amount of G⁶-Me in liver DNA did not differ significantly. We observed a decrease of G⁷-Me in the liver of the group treated with CCK together with POP as compared to POP alone (P < 0.005). Lower amounts of G⁶-Me were found in ductal preparations (P < 0.01) of the animals treated with CCK before POP as compared to POP alone. CCK also modified the pattern of alkylation in the acinar tissue, but without a clear relationship with the timing of adminstration. The results suggest that the inhibitory effect of CCK-8 on pancreatic carcinogenicity of BOP could be related to its capability to modify DNA alkylation by yet unknown mechanisms.