The research proposed is an analysis of published data on mutagenesis, particularly data on changes in base sequence at mutations induced by various agents, to learn more about mechanisms of mutagenesis and to identify mutagenic agents. Some of these data are available in a database at Yale, and some in databases organized elsewhere. Topics for study include: the mechanism of formation and the mutagenic specificity of mutants with two mutations, such as a frameshift with an accompanying base change, mutants with two (or more) well-separated base changes and the spectra of mutations induced by hydrogen peroxide, superoxide radical, and singlet oxygen. Databases for sequence changes found in cancer-related genes (such as p53) from human and animal tumors will be searched for patterns of mutation that, on the basis of the analyses, can suggest particular chemicals or physical agents as the cause of the tumors. A review of damage induced in DNA by oxidizing species, including ionizing radiation, also is planned. The Yale database of mutational sequence changes will be considerably enlarged during this work, and it is hoped that it can be incorporated as part of a sequence database such as Genbank.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA058952-06
Application #
2700496
Study Section
Chemical Pathology Study Section (CPA)
Program Officer
Pelroy, Richard
Project Start
1993-02-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
2000-04-30
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Hutchinson, F; Donnellan Jr, J E (1998) A mutation spectra database for bacterial and mammalian genes: 1998. Nucleic Acids Res 26:290-1
Hutchinson, F; Donnellan Jr, J E (1997) A mutation spectra database for bacterial and mammalian genes. Nucleic Acids Res 25:192-5
Hutchinson, F; Donnellan Jr, J E (1996) A general database for DNA sequence changes induced by mutagenesis of several bacterial and mammalian genes. Nucleic Acids Res 24:172-6
Hutchinson, F (1995) Analysis of deletions induced in the genome of mammalian cells by ionizing radiation. J Mol Biol 254:372-80
Hutchinson, F (1994) Induction of tandem-base change mutations. Mutat Res 309:11-5
Hutchinson, F; Donnellan Jr, J E (1994) Yale database for DNA sequence changes in mutagenesis. Nucleic Acids Res 22:3566-8