title: Dietary fish oil (MaxEPA) enhances pancreatic carcinogenesis in azaserine-treated rats.
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.
authors.affiliation: TNO Nutrition and Food Research Institute, Department of Pathology, Zeist, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Appel
authors.forename: R A
authors.initials: RA
authors.lastname: Woutersen
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000633:toxicity*; D001377:Azaserine; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D003043:Cocarcinogenesis; D004042:Dietary Fats, Unsaturated / Q000009:adverse effects*; D004281:Docosahexaenoic Acids; D004338:Drug Combinations; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D015118:Eicosapentaenoic Acid; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000633:toxicity*; D005260:Female; D005395:Fish Oils / Q000633:toxicity*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism; D011230:Precancerous Conditions / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004042:Dietary Fats, Unsaturated; D004338:Drug Combinations; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; C045153:Maxepa; D011453:Prostaglandins; D004281:Docosahexaenoic Acids; D001377:Azaserine; D015118:Eicosapentaenoic Acid