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 less than 0.005). Lower amounts of G6-Me were found in ductal preparations (P less than 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 administration. 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.
Corra
S
S
Department of Surgery, University of Verona, Ospedale Policlinico, Italy.
Kazakoff
K
K
Lawson
T A
TA
Adrian
T E
TE
Pour
P M
PM
D000478:Alkylation / Q000187:drug effects; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D008113:Liver Neoplasms / Q000139:chemically induced; D009602:Nitrosamines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology
D009602:Nitrosamines; D006147:Guanine; C013622:nitrosobis(2-oxopropyl)amine; C008450:7-methylguanine; D004247:DNA; D002766:Cholecystokinin; C008449:O-(6)-methylguanine; D012844:Sincalide