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 t he capability of sulfated CCK-8 to inhibit DNA alkylation in the hamst er pancreas. We examined the pattern of O6-methylguanine (G6-Me) and N 7-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). Th e 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 t issue, but without a clear relationship with the timing of administrat ion. The results suggest that the inhibitory effect of CCK-8 on pancre atic carcinogenicity of BOP could be related to its capability to modi fy DNA alkylation by yet unknown mechanisms.