Analyses will be carried out, with the use of a data bank of published data sets (more than 250 such sets to date), of changes in DNA base sequence induced by a variety of mutagens, to obtain information on mechanisms of mutagenesis. The data will be interpreted in light of present knowledge of the factors determining mutagenic specificity: formation of mutagenic products in the DNA, repair, and mutagenic processing of lesions during replication. In this work it will be feasible to make comparisons over a wider range of mutagenized genes and cell types than is usually done, and also re-evaluate earlier data in light of more recent results. The agents to be studied include spontaneous processes, ionizing radiation, and oxidizing species such as peroxides and superoxide. Other subjects of study include the formation of frameshifts with associated base change mutations by some mutagens, and the effects of repair on mutagenic specificity. Because of the complexity of the products formed by ionizing radiation, a 1985 review of this subject will be updated. Also, an attempt will be made to develop a better quantitative description of the products formed in intracellular DNA by ionizing radiation, in terms of fractal chemical kinetics.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA058952-01
Application #
3203046
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1993-02-01
Project End
1996-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Yale University
Department
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