The research aims to determine the relationship between UV-induced DNA damage and the kinds and location of induced mutations and cancer. These are fundamental questions in carcinogenesis, since mutations in specific genes clearly have a causal role in carcinogenesis, yet the molecular mechanisms by which such mutations occur are poorly understood. For example, a direct link between carcinogen-induced DNA damage and sequence changes has not yet been made in an endogenous gene. The research will focus on determining the sequence location of genetic damage, and the gene- specific and strand-specific repair of UV photoproducts in the HPRT gene and the p53 tumor suppressor gene of human cells that differ in capacity for excision repair. HPRT mutants will be obtained and the mutated HPRT gene will be sequenced. The location of the mutations will be compared with the location of the gene damage present initially and after periods of repair. The location of DNA damage in the p53 gene in skin (human and mouse) will be correlated with mutations in the p53 gene in tumors induced in nude mice skin by UV. The data will provide a direct comparison of the kinds and specific location of gene damage with UV induced mutations and cancer, and will investigate the role of DNA repair in the process.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA001747-02
Application #
2084394
Study Section
Cancer Institutional Fellowship Review Committee (CT)
Project Start
1993-08-01
Project End
1997-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Michigan State University
Department
Internal Medicine/Medicine
Type
Schools of Osteopathy
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824