This project proposes to investigate the repair of a particular DNA lesion induced by reactive oxygen species-induced oxidative damage, and investigate a possible link between oxygen free radical-induced mutagenesis and human cancer. The objective of this project is to identify and characterize the function of a cellular system dedicated to the repair of 5-hydroxy-2'-deoxycytidine (5-OHdC), a stable and potentially mutagenic product of oxidative damage to cytidine. This will be accomplished through the use of a double-stranded DNA template which contains a single 5-OHdC lesion at a specified site as a substrate for specific repair of 5-OHdC. Furthermore, the possibility that deficiencies in the repair of this oxidative lesion may be linked to carcinogenesis will be investigated by characterizing the repair of 5-OHdC in a human hereditary disorder characterized by hypersensitivity to oxygen.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA069732-02
Application #
2443233
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1997-07-01
Project End
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Washington
Department
Pathology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Jackson, A L; Loeb, L A (2001) The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res 477:7-21
Jackson, A L; Loeb, L A (2000) Microsatellite instability induced by hydrogen peroxide in Escherichia coli. Mutat Res 447:187-98
Jackson, A L; Newcomb, T G; Loeb, L A (1998) Origin of multiple mutations in human cancers. Drug Metab Rev 30:285-304
Jackson, A L; Chen, R; Loeb, L A (1998) Induction of microsatellite instability by oxidative DNA damage. Proc Natl Acad Sci U S A 95:12468-73
Order, S E; Sleeper, A M; Stillwagon, G B et al. (1990) Radiolabeled antibodies: results and potential in cancer therapy. Cancer Res 50:1011s-1013s