Repair of ionizing radiation induced damage in mammalian cell DNA is crucial to cell survival. Shoulders on mammalian cell radiation survival curves can be explained by invoking saturation of a repair process at higher doses. To probe this hypothesis, assays of damage are required which can be used at low radiation doses (within the shoulder) as well as high radiation doses. Such assays are proposed here which are effective down to 10 rads, these will be used to test for saturation of repair, measuring rates of repair of DNA single strand breaks, """"""""double strand breaks"""""""", and base damage as a function of radiation dose. To probe the significance of these three types of lesions in causing cell death or transformation, attempts will be made to inhibit the repair process and test the result of this inhibition on cell survival or transformation. Also procedures which have been shown to affect cell survival will be probed as to their effects on repair. It is hoped that the information gained from these studies of DNA damage and repair at low doses will be useful in (a) determining the cause of mammalian shouldered survival curves and (b) determining the DNA lesions causing cell death and transformation so that, with the knowledge of cell repair capacity, the hazards of low dose radiation can be extrapolated.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Method to Extend Research in Time (MERIT) Award (R37)
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Radiation Study Section (RAD)
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Limoli, C L; Wu, C C; Milligan, J R et al. (1997) Photochemical production of uracil quantified in bromodeoxyuridine-substituted SV40 DNA by uracil DNA glycosylase and a lysyl-tyrosyl-lysine tripeptide. Mutagenesis 12:443-7
Limoli, C L; Ward, J F (1995) Photochemical production of double-strand breaks in cellular DNA. Mutagenesis 10:453-6
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Ward, J F (1994) DNA damage as the cause of ionizing radiation-induced gene activation. Radiat Res 138:S85-8
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Dewey, W C; Thompson, L L; Trinh, M L et al. (1994) A charge-coupled-device camera image analysis system for quantifying DNA distributions in agarose gels after pulsed-field gel electrophoresis. Radiat Res 140:37-47
Jones, G D; Boswell, T V; Ward, J F (1994) Effects of postirradiation temperature on the yields of radiation-induced single- and double-strand breakage in SV40 DNA. Radiat Res 138:291-6
Limoli, C L; Ward, J F (1994) Response of bromodeoxyuridine-substituted Chinese hamster cells to UVA light exposure in the presence of Hoechst dye #33258: survival and DNA repair studies. Radiat Res 138:312-9
Milligan, J R; Aguilera, J A; Ward, J F (1993) Variation of single-strand break yield with scavenger concentration for the SV40 minichromosome irradiated in aqueous solution. Radiat Res 133:158-62

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