Effects of sandostatin and castration on pancreatic carcinogenesis in rats and hamsters.
The effects of treatment with the somatostatin analogue Sandostatin, separately and in combination with surgical castration, on the development of azaserine-induced lesions in rat pancreas and N-nitrosobis(2-oxopropyl)amine (BOP)-induced lesions in hamster pancreas were investigated. The animals were divided in 4 groups and treated as follows: (a) controls, injected s.c. with saline solution (0.9% NaCl); (b) orchiectomy directly after the last treatment with carcinogen; (c) Sandostatin (SMS 201-995) subcutaneously; (d) orchiectomy followed by treatment with Sandostatin. No significant suppressive effects on plasma EGF or IGF-I concentrations were noted after Sandostatin treatment, but plasma gastrin levels decreased slightly in the rats, not in the hamsters. In rats, Sandostatin treatment enhanced rather than inhibited growth of acidophilic atypical acinar cell nodules. In hamster pancreas, by contrast, Sandostatin inhibited the development of putative pre-neoplastic ductular lesions. There was no interaction between treatment with Sandostatin and surgical castration. It was concluded that Sandostatin, when administered prophylactically, has an inhibitory effect on the growth of putative pre-neoplastic ductular, but not acinar, lesions.
Meijers
M
M
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, The Netherlands.
Woutersen
R A
RA
van Garderen-Hoetmer
A
A
Bakker
G H
GH
de Jong
F H
FH
Foekens
J A
JA
Klijn
J G
JG
D000818:Animals; D001377:Azaserine; D002273:Carcinogens; D006224:Cricetinae; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D006133:Growth Substances / Q000097:blood; D006168:Guinea Pigs; D006728:Hormones / Q000097:blood; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines; D015282:Octreotide / Q000494:pharmacology*; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology*; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D006133:Growth Substances; D006728:Hormones; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; D001377:Azaserine; D015282:Octreotide