Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in mice.
BACKGROUND
Pancreatic ductal adenocarcinoma has a poor long-term prognosis. Experimental models are necessary to understand not only its biologic behavior, but also the early pancreatic lesions known as pancreatic intraepithelial neoplasia (PanIN) and to develop new treatments. The aim of this study was to evaluate pancreatic carcinogenesis induced by 7,12-dimethyl-1,2-benzanthracene (DMBA) implantation in mice according to the PanIN classification system.


METHODS
Ninety male, Mus musculus, CF-1 mice underwent a median laparotomy and 1 mg of DMBA was implanted into the proximal pancreas held in place by a purse-string suture. Mice were killed after 30 and 60 days after which the excised pancreata were fixed in formalin, embedded in paraffin, and stained with hematoxylin-eosin for histologic analysis. The specimens were evaluated blind by 2 pathologists for the presence of the following histology: normal ducts, reactive hyperplasia, PanIN-1A, PanIN-1B, PanIN-2, and PanIN-3, and adenocarcinoma.


RESULTS
In the 30-day group, pathologic evaluation showed 4 (17%) reactive hyperplasia, 16 (67%) PanIN lesions, and 4 (17%) adenocarcinomas. In the 60-day group, there were 10 (27%) specimens with reactive hyperplasia, 13 (35%) with PanIN lesions, and 14 (38%) with adenocarcinomas. The difference between groups was statistically significant (P<.05). All pancreata with adenocarcinoma had concomitant PanIN lesions.


CONCLUSIONS
The DMBA experimental model in mice induces PanIN lesions and ductal adenocarcinoma that have similar histology to that of human pancreatic cancer. This model may be useful for study of pancreatic carcinogenesis, particularly the molecular progression of early pancreatic ductal lesions.
Osvaldt
Alessandro B
AB
Research Center of Hospital de Clinicas de Porto Alegre, Medical Post-Graduation Program: Surgery, Medical School of Rio Grande do Sul Federal University, Porto Alegre, Brazil. osvaldt@terra.com.br
Wendt
Luiz R
LR
Bersch
Vivian P
VP
Backes
Ariane N
AN
de Cássia A Schumacher
Rita
R
Edelweiss
Maria I A
MI
Rohde
Luiz
L
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002278:Carcinoma in Situ / Q000139:chemically induced* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000473:pathology
D015127:9,10-Dimethyl-1,2-benzanthracene