An in vitro model of human pancreas carcinogenesis was developed in which carcinoma was induced by chemical carcinogens. Dimethylnitrosamine (DMN) and methylnitrosourea (MNU) were successfully used in this model to induce pancreatic carcinoma ranging from undifferentiated carcinoma to well-differentiated papillary carcinoma. Monoclonal antibodies to parenchymal cells were used to study the modulation of surface markers during carcinogenesis. A preneoplastic step, namely ductal metaplasia, was identified in this model before the development of hyperplasia, atypia and carcinoma. It is proposed to develop antibodies specific for progenitor cells of cancer. It is further proposed to examine the effects of NNK, a tobacco-specific carcinogen on human pancreas explants. In addition to morphological studies (light microscopy), it is proposed to quantitate and relate the rate of removal of 06-methylguanine from cells in pancreas organ culture with DMN- and NNK-induced carcinoma. The availability of normal and DMN- and NNK-treated pancreas explants at various stages of carcinoma induction facilitates the development of antibodies against cell markers specific for each of the steps in carcinogenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA022682-09
Application #
3165880
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1979-08-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
Type
Schools of Medicine
DUNS #
068552207
City
Brooklyn
State
NY
Country
United States
Zip Code
11203