Dietary fish oil (MaxEPA) enhances pancreatic carcinogenesis in azaserine-treated rats

In the present study the putative chemopreventive effect of dietary fish oil (MaxEPA) on azaserine-induced pancreatic carcinogenesis in rats was investigated, Groups of rats were maintained on a semipurified low-fat (LF; 5 wt%) diet or on semipurified high-Fat (HF; 25 wt%) diets containing 5 wt% linoleic acid (LA) and including 0.01 1.2, 2.4, 4.7, 7.1 or 9.4 wt% MaxEPA. Animals fed a HF diet developed significantly higher mean numbers of atypical acinar cell nodules (AACNs), adenomas and carcinomas than animals fed a LF diet. Dietary MaxEPA caused a significant (P<0.01) dose-related increase in mean number of AACNs (0.5 < (empty set) < 3.0 mm). The mean number of adenomas and carcinomas remained similar among the groups. Cell proliferation was significantly lower in AACNs from animals fed HF containing 9.4% MaxEPA in comparison with HF without MaxEPA and with LF. LA levels had increased and arachidonic acid (AA) levels had decreased in blood plasma and pancreas with increasing dietary MaxEPA. Feeding MaxEPA resulted in significant decreases in 6-keto-prostaglandin (PG) F-1 alpha (P< 0.05) and PGF(2 alpha) (P< 0.01) in non-tumorous pancreas, whereas PGF(2), PGF(2 alpha) and thromboxane B-2 (TXB(2)) levels were significantly (P< 0.001) higher in pancreatic tumour tissue than in non-tumorous pancreatic tissue. It is concluded that (i) dietary MaxEPA enhances dose-relatedly growth of putative preneoplastic AACNs in the pancreas of azaserine-treated rats; (ii) dietary MaxEPA inhibits the conversion of LA to AA, as well as the conversion of AA to TXB(2) or PGF(2 alpha) in non-tumorous pancreatic tissue; (iii) the high levels of PGE(2), PGF(2 alpha) and TXB(2) in pancreatic adenocarcinomas indicate a possible role for these eicosanoids in modulation of tumour growth.