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 F1 alpha, prostaglandin F2 alpha and thromboxane B2 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.
Department of Biological Toxicology, TNO Nutrition and Food Research, Zeist, The Netherlands.
M J
MJ
Appel
R A
RA
Woutersen
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001377:Azaserine; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004041:Dietary Fats / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005395:Fish Oils / Q000627:therapeutic use*; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000633:toxicity; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D004041:Dietary Fats; D005227:Fatty Acids; D005395:Fish Oils; D008041:Linoleic Acids; D011453:Prostaglandins; D001377:Azaserine; D019787:Linoleic Acid