Effects of a diet high in fish oil (MaxEPA) on the formation of micronucleated erythrocytes in blood and on the number of atypical acinar cell foci Induced in rat pancreas by azaserine.
The present study was performed to investigate the influence of fish oil on the genotoxic effects of azaserine, using the formation of micronucleated erythrocytes as a measure for the degree of initiating potency and the number and size of putative preneoplastic pancreatic atypical acinar cell foci (AACF) as a measure for the actual number of initiated cells. Male Wistar rats were treated twice i.p. with 30 mg azaserine per kg body weight to induce AACF. During the initiation/early promotion phase the rats were maintained on diets containing 5 wt% vegetable oil (safflower and high-oleic sunflower oil), 25 wt% vegetable oil, 25 wt% fat (15% vegetable oil + 10 wt% fish oil), or 25 wt% fat (5% vegetable oil + 20 wt% fish oil), respectively. One day after carcinogen treatment, the numbers of micronucleated polychromatic erythrocytes were determined in blood smears obtained from 10 animals per group. Each high-fat diet resulted in higher percentages of micronucleated polychromatic erythrocytes than the low-fat diet. Dietary fish oil did not significantly influence the number of micronucleated cells. Two weeks after carcinogen treatment, the diets containing fish oil were replaced by the diet containing 25% vegetable oil, and the animals were further maintained for about 14 wk. Pancreatic tissue slides were microscopically evaluated for the number and size of AACF. Dietary fish oil caused an increase in the number and size of AACF, although a clear dose-effect relationship was absent. It was concluded that a high level of dietary fish oil, when given during the induction/early promotion phase, enhances azaserine-induced pancreatic carcinogenesis in rats.
Appel
Marko J
MJ
Department of General Toxicology, TNO Nutrition and Food Research, PO Box 360, 3700 AJ Zeist, The Netherlands. Appel@voeding.tno.nl
Woutersen
Ruud A
RA
D000818:Animals; D001377:Azaserine / Q000008:administration & dosage*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D004912:Erythrocytes / Q000648:ultrastructure*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000139:chemically induced; D010938:Plant Oils / Q000008:administration & dosage; D011230:Precancerous Conditions / Q000097:blood / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar
D004042:Dietary Fats, Unsaturated; D004338:Drug Combinations; D005395:Fish Oils; C045153:Maxepa; D010938:Plant Oils; D004281:Docosahexaenoic Acids; D001377:Azaserine; D015118:Eicosapentaenoic Acid