Effects of octreotide, a somatostatin analogue, on initiation of pancreatic carcinogenesis in hamsters with N-nitrosobis(2-oxopropyl)amine.
The modifying effects of octreotide acetate, a somatostatin (SMS) analogue shown to inhibit secretion of digestive enzymes, bicarbonate and pancreatic juice, on the initiation phase of pancreatic carcinogenesis were investigated in hamsters simultaneously treated with N-nitrosobis(2-oxopropyl)amine (BOP). Groups 1-3, each consisting of 20 animals, were given BOP subcutaneously once a week three times at a dose of 10 mg/kg body weight during administration of octreotide acetate for 28 days via osmotic pumps implanted subcutaneously at doses of 6 microg/day (group 1), 3 microg/day (group 2) or 0 microg/day (saline) (group 3). Group 4-6 animals (each group ten animals) were similarly administered octreotide acetate for the same period with five subcutaneous injections of saline. At the termination of experimental week 40, the incidences and multiplicities of pancreatic ductal adenocarcinomas and dysplastic lesions did not significantly differ among groups 1-3. No neoplastic lesions were found in groups 4-6. Subcutaneous administration of octreotide acetate resulted in obviously increased plasma octreotide levels. Our results thus suggest that this SMS analogue may not modulate the initiation of BOP-induced pancreatic carcinogenesis, regardless of its pharmacological action.
Furukawa
F
F
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan. furukawa@nihs.go.jp
Nishikawa
A
A
Nakamura
H
H
Miyauchi
M
M
Son
H
H
Hirose
M
M
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D005260:Female; D007279:Injections, Subcutaneous; D008647:Mesocricetus; D009602:Nitrosamines / Q000633:toxicity*; D015282:Octreotide / Q000097:blood / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control
D018931:Antineoplastic Agents, Hormonal; D002273:Carcinogens; D009602:Nitrosamines; C031443:N-nitrosobis(2-oxobutyl)amine; D015282:Octreotide