Abstract
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 0.0, 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 < phi < 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) F1 alpha (P < 0.05) and PGF2 alpha (P < 0.01) in non-tumorous pancreas, whereas PGE2, PGF2 alpha and thromboxane B2 (TXB2) 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-relatively 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 TXB2 or PGF2 alpha in non-tumorous pancreatic tissue; (iii) the high levels of PGE2, PGF2 alpha and TXB2 in pancreatic adenocarcinomas indicate a possible role for these eicosanoids in modulation of tumour growth.
Highlights
Information on effects of fish oil on pancreatic carcinogenesis is scarce and comes mainly from the studies of O'Connor et al (1985), who observed that in azaserine-treated rats maintained on a 20% menhaden oil (MO) diet for 4 months, the number and size of pancreatic preneoplastic atypical acinar cell nodules (AACNs) were significantly reduced as compared with rats fed a 20% corn oil (CO) diet
Using the same model, we did not find any difference in AACN yield in rats fed 25% fat diets with a constant 5% linoleic acid (LA) level, either or not containing 9.4% fish oil (MaxEPA), for 6 months (Appel and Woutersen, 1994)
LA (C 18:2) levels in microsomes from tumours were significantly lower in all diet groups measured (P
Summary
Using the same model, we did not find any difference in AACN yield in rats fed 25% fat diets with a constant 5% linoleic acid (LA) level, either or not containing 9.4% fish oil (MaxEPA), for 6 months (Appel and Woutersen, 1994).
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