The overall objective of this project is to obtain information on specific types of radiation-induced DNA base lesions and their biological consequences in vivo and in vitro. The quantities and types of base lesions will be determined in the DNA of bacterial strains selected for their known sensitivities to ionizing radiation and for their genetically characterized ability to repair radiation damage. Specific base lesions will be identified and quantitated by various kinds of chromatography including HPLC, and 13C-NMR as a function of radiation dose, level of survival, and time after irradiation during the period in which radiation damage to DNA is though to be repaired. Monoclonal antibody assays will be developed for specific base lesions to enable their detection at low, biologically relevant doses. The effects of the hydroxyl radical, oxygen, radioprotective and radiosensitizer compounds on the types and quantities of base damage will be determined. From studies involving model systems in vitro, the relationships between damage to DNA bases and mutagenesis will be delineated. Certain in vitro studies on the effects of radiation on DNA base and sugar constituents will be carried out when the data from such studies are needed to interpret in vivo results and cannot be found in available literature. The information obtained from this project will make available more substantive data on the destruction of DNA bases as it occurs in vivo by ionizing radiation. These data also will allow, for the first time, a direct assessment of the applicability of much of the previous research on the radiation chemistry of DNA and its constituents in vitro to actual in vivo damage. New insights may be provided into the chemical basis for the oxygen effect and for the modification of radiation response by various compounds with potential application in cancer radiotherapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043324-02
Application #
3185536
Study Section
Radiation Study Section (RAD)
Project Start
1985-11-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Claycamp, H G; Luo, D (1994) Plutonium-catalyzed oxidative DNA damage in the absence of significant alpha-particle decay. Radiat Res 137:114-7
Claycamp, H G; Huang, H (1993) Zinc deficiency in antibody-conjugated alkaline phosphatase inhibits enzyme activity in ELISAs. Biotechniques 14:348-50
Claycamp, H G; Ho, K K (1993) Background and radiation-induced 8-hydroxy-2'-deoxyguanosine in gamma-irradiated Escherichia coli. Int J Radiat Biol 63:597-607
Huang, H; Claycamp, H G (1993) DNA excision repair as a component of adaptation to low doses of ionizing radiation in Escherichia coli. Int J Radiat Biol 64:613-9
Claycamp, H G (1992) Phenol sensitization of DNA to subsequent oxidative damage in 8-hydroxyguanine assays. Carcinogenesis 13:1289-92
DeRose, C M; Claycamp, H G (1991) Oxidative stress effects on conjugational recombination and mutation in catalase-deficient Escherichia coli. Mutat Res 255:193-200
Claycamp, H G; McCormick, M L; DeRose, C M et al. (1990) Superoxide dismutase and media dependence of far-UV radiation resistance in thiol-treated cells. Int J Radiat Biol 58:449-61
Claycamp, H G; DeRose, C M (1990) The dependence of thiol-inducible radiation resistance in Escherichia coli K12 on the medium and catalytic metal. Radiat Res 124:266-72
Claycamp, H G; Ho, K K; DeRose, C (1990) Thiol and hydrogen peroxide modification of recA induction in UV-irradiated wild-type and catalase-deficient Escherichia coli K12. Mutat Res 235:101-9
DeRose, C; Claycamp, H G (1989) Dimethylformamide-induced changes in the radiation survival of low- and high-passage intestinal epithelial cells (IEC-17) in vitro. Radiat Res 118:269-82

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