Abstracts
1999 Digestive Disease Week

# 2145 A HIGH FAT, HIGH-PROTEIN DIET PROMOTES CARCINOGENESIS IN A RAT MODEL OF DUCTAL PANCREATIC ADENOCARCINOMA
Kaspar Z'graggen, MA Gen Hosp and Harvard Med Sch, Boston, MA; Jens Werner, MA Gen Hosp, Boston, MA; Ramon E Jimenez, Fiona Graeme-Cook, MA Gen Hosp; Jaime A Rivera, Andrew L Warshaw, Carlos Fernandez-del Castillo

We recently characterized a carcinogen-induced rat model of ductal pancreatic adenocarcinoma. High dietary content of fat and protein has been hypothesized to promote pancreatic carcinogenesis and we studied the effect of such a diet on the prevalence of dimethylbenzanthracene (DMBA)-induced pancreatic cancer after one and over 9 months. Methods:DMBA (5mg) was implanted into the head of the pancreas of rats. Two weeks before the procedure, groups of 310 and 50 rats were randomly allocated to receive a normal laboratory diet (ND) or a highfat/high protein diet (HFPD). The group of 310 rats was killed after 9 months or earlier if moribund; the group of 50 rats was killed after one month. Multiple histotological sections of each pancreas were assessed by an experienced pathologist. Results: The 30-day mortality in the subgroup sacrificed at one month was 8%(2/25 each). In the 9-months study the cumulative mortality was 41.3%(ND; 64/155) and 40.6%(HFPD; 63/155). In rats sacrificed at one month the prevalence of microscopic ductal pancreatic adenocarcinoma (carcinoma-in-situ and microinvasive cancers) was 22%(ND; 5/23) and 13%(HFPD; 3/23)(p=0.32). All cancers arose from small pancreatic ducts at the implant site as determined histologically and by IHC. Over the 9-month period the prevalence of pancreatic ductal adenocarcinoma was significantly higher (29%; 45/155) in the HFPD group compared with the ND group(16.7%;26/155)(p=0.2) The prevalence of ductal cancer increased in the HFPD groups from 13% to 34% (p=0.05) but was identical at one and 9 months (22%; p=0.98) in the ND groups. Conclusion: This study indicates that a high fat, high protein diet promotes pancreatic carcinogenesis in the DMBA rat model of ductal adenocarcinomas.

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