Effects of dietary galactooligosaccharide on azaserine-induced acinar pancreatic carcinogenesis in male Wistar rats.
In the present study the effects of dietary galactooligosaccharide (GOS) on dietary fat-promoted pancreatic carcinogenesis in azaserine-treated rats were investigated. The aims of this study were to determine 1) whether GOS acts as an inhibitor of pancreatic carcinogenesis and 2) whether GOS interacts with dietary fat-promoted pancreatic tumor development. Four groups of 39 azaserine-treated rats were maintained on different experimental diets that were formulated as follows: 4.3 wt% fat-8.3 wt% GOS (low fat-low GOS), 3.5 wt% fat-27.4 wt% GOS (low fat-high GOS), 15.5 wt% fat-9.5 wt% GOS (high fat-low GOS), and 14.3 wt% fat-28.6 wt% GOS (high fat-high GOS). Autopsies were performed after 6 months (9 animals/group) and 12 months (30 animals/group). Five rats per group were treated with bromodeoxyuridine before autopsy. Parallel sections of the pancreas were stained with hematoxylin and eosin or with hematoxylin and a monoclonal antibody against bromodeoxyuridine and examined by light microscopy. A high-fat diet caused a significant decrease, whereas a diet high in GOS caused a significant increase, in absolute and relative weight of the cecum content. A high level of dietary fat caused a highly significant increase in multiplicity and incidence of pancreatic (pre)neoplastic lesions after 6 and 12 months of feeding. A high level of GOS in the diet did not influence the number of atypical acinar cell nodules or the tumor incidence in comparison with controls. Dietary fat and dietary GOS caused a significant increase in cell proliferation in atypical acinar cell nodules after six months. It was concluded that dietary GOS has no modulating effect on pancreatic carcinogenesis in azaserine-treated rats or on the tumor-promoting effect of a high-fat diet.
Appel
M J
MJ
Department of General Toxicology, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Wijnands
M V
MV
Woutersen
R A
RA
D000818:Animals; D001377:Azaserine; D002432:Cecum / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004032:Diet; D004041:Dietary Fats / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000178:diet therapy*; D051381:Rats; D017208:Rats, Wistar; D014312:Trisaccharides / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D004041:Dietary Fats; D014312:Trisaccharides; D001377:Azaserine