Abstract

The broad objective of the present proposal is to determine whether different classes of environmentally-relevant carcinogens form different DNA adduct spectrums and distributions within the different structural regions of human chromatin, and whether these adducts alter the transitions between the different structural states of the chromatin fiber. Specifically, we plan to: (1) characterize the distribution and types of DNA and protein adducts formed by different classes of carcinogens within long chromatin fragments in vitro that mimic the different structural states and compositions of the chromatin fiber in vivo; (2) determine whether the chromatin fiber structure can be altered by the formation of adducts from different classes of carcinogens; (3) determine whether such alterations affect the structural transitions of the chromatin fiber; and (4) use these damaged, """"""""model"""""""" chromatin fibers as substrates for damage specific endonucleases in vitro. These studies should lead the way for a careful, systematic analysis of the effects of DNA adduct variation, chromatin fiber structure and chromatin fiber composition on the competency of excision repair enzymes in vitro.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003720-03
Application #
3251299
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1986-09-16
Project End
1992-02-29
Budget Start
1990-03-01
Budget End
1992-02-29
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Washington State University
Department
Type
Schools of Arts and Sciences
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164