Promoting effect of a high-fat/high-protein diet in DMBA-induced ductal pancreatic cancer in rats

Citation
K. Z'Graggen et al., Promoting effect of a high-fat/high-protein diet in DMBA-induced ductal pancreatic cancer in rats, ANN SURG, 233(5), 2001, pp. 688-694
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Surgery,"Medical Research Diagnosis & Treatment
Journal title
ANNALS OF SURGERY
ISSN journal
0003-4932 → ACNP
Volume
233
Issue
5
Year of publication
2001
Pages
688 - 694
Database
ISI
SICI code
0003-4932(200105)233:5<688:PEOAHD>2.0.ZU;2-0
Abstract
Objective To investigate whether a high-fat/high-protein diet (HFPD) acts a s a promoter of the natural course of cancer growth in the 7,12-dimethylben zanthracene (DMBA)-induced ductal pancreatic cancer model in rats. Summary Background Data DMBA implantation to the rat pancreas induces ducta l adenocarcinoma. Information regarding the effects of diet and the presenc e of K-ras mutation in this model is not available. Methods Rats were rando mly assigned to regular rat chow or a diet with a 30% content in fat and pr otein (HFPD). The presentation of cancer, the histologic spectrum of neopla sia at 1 and 9 months, and the prevalence of cancer in relation to diet wer e assessed. Histologic specimens comprising normal ducts, hyperplasia, dysp lasia/carcinoma in situ, or carcinoma were designated by a pathologist and microdissected. Genomic DNA was extracted. and K-ras and H-ras gene mutatio ns were determined by a mutant-enriched polymerase chain reaction assay and direct sequencing. Results Rats fed HFPD increased their weight significantly compared with co ntrols. DMBA induced characteristic stages of neoplasia at the implant site but not elsewhere. Macroscopic cancers of the pancreatic head presented re gularly with common bile duct and gastric outlet obstruction. The prevalenc e of K-ras mutations was proportional to the degree of epithelial abnormali ty. K-ras mutations were significantly more frequent in cancer than in norm al and hyperplastic ducts. H-ras mutations were not found. At 1 month in th e HFPD-fed rats, the prevalence of cancer (16%) and dysplasia (16%) was not significantly different from the prevalence of cancer (29%) and dysplasia (8%) in the chow-fed rats. At 9 months the prevalence of cancer in the HFPD -fed rats increased to 29%, whereas that in the chow-fed rats decreased to 17%. The combined prevalence of cancer and dysplasia at 9 months in the HFP D-fed rats (34%) significantly exceeded that in the chow-fed rats. Conclusions DMBA induces characteristic stages of neoplasia in the evolutio n of ductal pancreatic cancer in rats. K-ras mutations occur progressively in the ladder of oncogenesis, as in human pancreatic neoplasms. The additio n of a diet with a high fat and protein content acts as a promoter of carci nogenesis, possibly by interfering with repair mechanisms and natural regre ssion of early lesions.