The major thrust of this reseach is to continue the systematic investigation of intraspecies differences in the metabolism of certain Beta-oxidized notrosamine carcinogens, such as N-nitroso-2,6-dimethylomorpholine (NNDM), N-nitrosobis(2-oxopropyl)-amine (BOP), and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) which exhibit marked differences in carcinogenic potency and organotropy between the rat and hamster. These involve in vivo and in vitro studies in Syrian golden hamsters and Fischer 344 rats treated with NNDM, BOP and HPOP, and include 1) their in vivo metabolism including formation of the putative proximate carcinogens MOP and MHP; 2) the pharmaco-kinetics of their uptake and excretion; 3) formation and identification of major adducts in liver and pancreas; 4) metabolism in primary pancreatic acinar cell and hepatocyte cultures; 5) their in vitro metabolism by subcellualr fractions; 6) their activation by isolated hepatocytes to mutagenic metabolites as assayed by the V79 cell system and the capacity of ancinar and liver cells to repair DNA damage as measured by unscheduled DNA repair; 7) the uptake of BOP and HPOP by isolated pancreatic ancinar cells and their binding to DNA and RNA; and 8) a test of the hypothesis that sulfate ester formation of HPOP may be important in its activation by determining whether modulation of the sulfate pool significantly alters the yield of tumor induced by HPOP in hamsters.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034051-08
Application #
3171785
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1983-02-01
Project End
1991-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Scarpelli, D G; Cerny, W L; Mangold, K A (1992) Gene alterations in rodent and human tumors of the exocrine and endocrine pancreas. Prog Clin Biol Res 376:223-43

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