Effects of castration, alone and in combination with aminoglutethimide, on growth of (pre)neoplastic lesions in exocrine pancreas of rats and hamsters.
We studied the effects of hormonal manipulation by orchiectomy, alone or in combination with the aromatase inhibitor aminoglutethimide (AGT), and by luteinizing hormone-releasing hormone agonist (LH-RH-A) (goserelin) treatment on the development of early putative (pre)neoplastic lesions induced in the pancreas of rats and hamsters by azaserine and N-nitrosobis(2-oxopropyl)amine respectively. Treatment of the animals started 1 week after the last injection with carcinogen and continued for 4 months. Orchiectomy caused a significant inhibition of growth of acidophilic atypical acinar cell nodules in the rat model, whereas surgical castration did not show an effect in the hamster model. In rats, but not in hamsters, orchiectomy resulted in a significant decrease in body weight and in absolute, but not relative pancreatic weight. Treatment of the animals with AGT or goserelin did not cause a significant effect on the development of either putative preneoplastic acinar lesions in rat pancreas or early ductular lesions in hamster pancreas. Hamsters showed clearly higher plasma epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) concentrations than rats, while plasma testosterone levels were significantly lower. Plasma EGF and IGF-1 levels decreased with increasing age in both control and treatment groups. Compared to controls there were no clear unequivocal effects of treatment on EGF, IGF-1 and gastrin levels. Plasma testosterone levels decreased by orchiectomy and LH-RH-A treatment. In rats hormone-induced effects on food intake and altered nutritional status might be important with respect to the development of carcinogen-induced preneoplastic pancreatic lesions.
Meijers
M
M
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, 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
D000616:Aminoglutethimide / Q000494:pharmacology*; D000818:Animals; D001377:Azaserine / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D002064:Buserelin / Q000031:analogs & derivatives / Q000494:pharmacology; D002273:Carcinogens; D006224:Cricetinae; D004815:Epidermal Growth Factor / Q000097:blood; D005755:Gastrins / Q000097:blood; D017273:Goserelin; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines / Q000633:toxicity; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000503:physiopathology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000032:analysis; D013739:Testosterone / Q000097:blood
D002273:Carcinogens; D005755:Gastrins; D009602:Nitrosamines; D013002:Somatomedins; D017273:Goserelin; D000616:Aminoglutethimide; D013739:Testosterone; C013622:nitrosobis(2-oxopropyl)amine; D004815:Epidermal Growth Factor; D001377:Azaserine; D002064:Buserelin