MODULATION OF GROWTH AND CELL TURNOVER OF PRENEOPLASTIC LESIONS AND OF PROSTAGLANDIN LEVELS IN RAT PANCREAS BY DIETARY FISH-OIL

In the present study the modulating effects of dietary fish oil (MaxEPA) on unsaturated fat-promoted pancreatic carcinogenesis in azaserine-treated rats were investigated. Three groups of 20 rats (each group comprised five saline-treated and 15 azaserine-treated animals) were fed an AIN76-based purified diet containing (i) 5 wt% fat, (ii) 25 wt% fat including 5 wt% linoleic acid or (iii) 25 wt% fat including 5 wt% linoleic acid and 9.4 wt% (20 cal%) MaxEPA for 6 months. The number and size of pancreatic atypical acinar cell foci was significantly higher (P < 0.01) in azaserine-treated animals maintained on a high fat diet than in those fed a low fat diet. MaxEPA did not influence the promoting effect of the high fat diet. The labeling index of atypical acinar cell foci in animals maintained on both a low fat or a high fat/MaxEPA diet was significantly (P < 0.01) lower than that in rats fed a high fat diet without MaxEPA. The linoleic acid concentration was higher, whereas the arachidonic acid concentration was lower, in blood plasma and to a lesser extent also in the pancreas of animals given MaxEPA in comparison with the other groups. Furthermore, animals fed MaxEPA showed lower 6-keto-prostaglandin F-1 alpha, prostaglandin F-2 alpha and thromboxane B-2 levels, but not prostaglandin E2 levels in pancreatic tissue in comparison with the other groups. It is concluded that a high fat diet containing 5 wt% linoleic acid has a strong promoting effect on pancreatic carcinogenesis in azaserine-treated rats, Dietary MaxEPA did not influence the promoting effect of unsaturated fat on pancreatic carcinogenesis, although it caused a decrease in both cell proliferation in atypical acinar cell foci and prostaglandin levels in the pancreas.