Dietary fish oil (MaxEPA) enhances pancreatic carcinogenesis in azaserine-treated rats
article
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 <θ <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(1α), (P<0.05) and PGF(2α) (P<0.01) in non-tumorous pancreas, whereas PGE2, PGF(2α) 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-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 TXB2 or PGF(2α) in non-tumorous pancreatic tissue; (iii) the high levels of PGE2, PGF(2α), and TXB2 in pancreatic adenocarcinomas indicate a possible role for these eicosanoids in modulation of tumour growth. Chemicals/CAS: Anticarcinogenic Agents; Azaserine, 115-02-6; Carcinogens; Dietary Fats, Unsaturated; Docosahexaenoic Acids, 25167-62-8; Drug Combinations; Eicosapentaenoic Acid, 1553-41-9; Fatty Acids; Fatty Acids, Omega-3; Fish Oils; Maxepa; Prostaglandins
Topics
AnimalsAnticarcinogenic AgentsAzaserineBody WeightCarcinogensCell DivisionCocarcinogenesisDietary Fats, UnsaturatedDocosahexaenoic AcidsDrug CombinationsDrug SynergismEatingEicosapentaenoic AcidFatty AcidsFatty Acids, Omega-3FemaleFish OilsLiverOrgan SizePancreatic NeoplasmsPrecancerous ConditionsPregnancyProstaglandinsRatsRats, Wistar
TNO Identifier
69541
ISSN
00070920
Source
British Journal of Cancer, 73(1), pp. 36-43.
Pages
36-43