# PANCREATIC DUCT CARCINOGENS--SPECIES DIFFERENCES

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1992 · $212,227

## Abstract

Oxidized derivatives of dipropylnitrosamine administered to the Syrian
golden hamster induce adenocarcinoma of the pancreatic ducts bearing a
strong morphologic and biological resemblance to its counterpart in humans.
Since carcinomas of the exocrine pancreas in particular those arising in
ducts represent the most prevalent form of pancreatic cancer in humans,
this model has been the focus of considerable research.  Important findings
obtained from its study that meant further consideration include the
biological significance of the limited activation of these from its study
that merit further consideration include the biological significance of the
limited activation of these carcinogens by the pancreas as compared to
liver, and the high resistance of the pancreatic ducts of the rat to
chemical carcinogenesis.  In addition, pancreatic duct cells which
represent only 4% of the cell population of the pancreas have not until
recently been successfully maintained in culture for extended periods so
that detailed analysis of the genetic and functional events involved in
their neoplastic transformation is now possible.  In view of the foregoing,
we propose to investigate the following testable hypotheses:  that
intrapancreatic metabolism of carcinogen by acinar and duct cells plays a
role in pancreatic carcinogenesis, that the susceptibility of pancreatic
ducts in the hamster and their resistance in the rat are attributable to
differences in DNA damage and repair, that a series of definable key
intracellular events and adaptive cellular changes occur during the
malignant transformation of duct cells, that the cooperativity of various
immortalizing and transforming oncogenes depend on their relative levels of
expression and perhaps sequence of activation, and that important hitherto
unrecognized genes remain to be identified in pancreatic ductal
carcinogenesis.  The major specific aims of this project are:  1) To
identify and characterize the 15 and 17KD proteins secreted by normal
hamster pancreatic duct cell monolayers and determine their tissue
distribution and expression during ontogenesis of the pancreas and liver;
2) To ascertain if duct cells alone or cocultured with acinar or liver
cells can undergo mutation following exposure to direct or indirect acting
carcinogens; 3) To compare DNA damage by direct or indirect acting
carcinogens and its repair in cultured hamster pancreatic duct cells with
those of a rat; 4) To identify the sequence of genetic cytologic and
functional phenotypic alterations that occur in hamster duct cells
following exposure to methylnitrosourea (MNU), or (2-hydroxyptopyl)
nitrosourea (HPNU); 5) To characterize the cooperativity of various
immortalizing and transforming oncogenes in malignant transformation by
transfecting them at different levels of expression into normal hamster
pancreatic duct cells; and 6) To identify the genes that are expressed
and/or not expressed in the neoplastic transformation of hamster duct cells...

## Key facts

- **NIH application ID:** 3171786
- **Project number:** 5R01CA034051-10
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** DANTE G. SCARPELLI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $212,227
- **Award type:** 5
- **Project period:** 1983-02-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171786

## Citation

> US National Institutes of Health, RePORTER application 3171786, PANCREATIC DUCT CARCINOGENS--SPECIES DIFFERENCES (5R01CA034051-10). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3171786. Licensed CC0.

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