Azaserine-induced pancreatic carcinogenesis in rats: promotion by a diet rich in saturated fat and inhibition by a standard laboratory chow.
Dietary fat has been shown to enhance pancreatic carcinogenesis. Uncertainty still exists whether the amount of linoleic acid or the amount of fat is the main determining factor. In the present study the effects of a high lard, a low lard, a linoleic acid supplemented low lard and a laboratory chow diet were investigated on the development of (pre)neoplastic pancreatic lesions in rats treated with azaserine. The rats were killed 15 months after carcinogen treatment and the pancreata were examined for the number and size of putative preneoplastic lesions and for the occurrence of neoplasms. The linoleic acid supplemented low lard group showed a significantly increased number of basophilic foci as compared to the low lard group. Rats maintained on the linoleic acid supplemented diet or the laboratory chow developed significantly less atypical acinar cell nodules larger than 1.0 mm in diameter and adenocarcinomas as compared to the high lard group. Animals maintained on the low lard diet developed significantly less adenocarcinomas than rats on the high lard diet did. Overall, the number of benign and malignant pancreatic tumours was consistently higher in the high lard group and consistently lower in the linoleic acid supplemented low lard group than the number of these types of tumours in the low lard group, with the exception of the number of carcinomas in situ, which was lower in the high lard group. The laboratory chow group showed a significant lower number of atypical acinar cell nodules with a diameter over 1.0 mm and a lower number of adenocarcinomas as compared to both the high lard and the low lard group. It is concluded that a diet high in saturated fat has a promoting and that laboratory chow has an inhibitory effect on pancreatic carcinogenesis in azaserine-treated rats.
Appel
M J
MJ
Department of Biological Toxicology, TNO-CIVO Toxicology and Nutrition Institute, Zeist, The Netherlands.
nan Garderen-Hoetmer
A
A
Woutersen
R A
RA
D000818:Animals; D001377:Azaserine / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004032:Diet / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects*; D004435:Eating; D015994:Incidence; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000033:anatomy & histology / Q000166:cytology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D051381:Rats; D011919:Rats, Inbred Strains
D004041:Dietary Fats; D008041:Linoleic Acids; D001377:Azaserine; D019787:Linoleic Acid