Effects of dietary fish oil (MaxEPA) on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinogenesis in hamsters.
In the present study the chemopreventive potential of 25% fat (HF) diets containing 2 wt% linoleic acid (LA) and including 0.0, 1.2, 2.4, 4.7, 7.1 or 9.4 wt% dietary fish oil (MaxEPA) has been investigated using the N-nitrosobis(2-oxopropyl)amine (BOP)-hamster model for pancreatic cancer. The number of pancreatic borderline lesions (BLL) was significantly higher (P < 0.05) in the HF groups containing 1.2, 2.4 or 9.4 wt% MaxEPA in comparison with the HF group without MaxEPA. MaxEPA inhibited the metabolism of LA to arachidonic acid (AA) and of AA to prostaglandins (PGs) in both blood plasma and pancreatic microsomes. The pancreatic levels of PGE2 (P < 0.05), 6-keto-PGF1 alpha (P < 0.01) and PGF2 alpha (P < 0.05) decreased significantly with increasing dietary MaxEPA. The levels of PGE2 (P < 0.001), 6-keto-PGF1 alpha (P < 0.05), PGF2 alpha (P < 0.001) and thromboxane (TX) B2 (P < 0.001) in pancreatic adenocarcinomas were higher than in non-tumorous pancreas. The MaxEPA had no significant effect on the BrdU labeling index (LI) in acinar, ductular or centroacinar cells, nor on the LI in BOP-induced pancreatic lesions. It is concluded that (i) dietary fish oil has a slight enhancing effect on BOP-induced pancreatic carcinogenesis in hamsters and (ii) dietary fish oil dose-dependently inhibits the conversion of LA to AA and of AA to certain PGs and (iii) dietary fish oil does not influence the cell proliferation in hamster pancreas.
Appel
M J
MJ
Department of Pathology, TNO Nutrition and Food Research Institute, Zeist, The Netherlands.
Woutersen
R A
RA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002273:Carcinogens; D002455:Cell Division; D006224:Cricetinae; D015232:Dinoprostone / Q000378:metabolism*; D005395:Fish Oils / Q000008:administration & dosage*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control
D002273:Carcinogens; D005395:Fish Oils; D008041:Linoleic Acids; D009602:Nitrosamines; D016718:Arachidonic Acid; C013622:nitrosobis(2-oxopropyl)amine; D019787:Linoleic Acid; D015232:Dinoprostone