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Damage, Repair, and DNA Synthesis in Radiation Lethality of Mammalian Cells

  • M. M. Elkind
  • H. Utsumi
  • M. Hagan
  • E. Ben-Hur
Chapter

Abstract

A number of lines of evidence implicate nuclear DNA, or nuclear structures containing genomic DNA, in mammalian cell killing by ionizing radiation. Among these are the sensitizing effect when thymine in DNA is partially replaced by a halogenated pyrimidine, the enhancement of cell killing which results from the pre- or postirradiation treatment with the DNA intercalator actinomycin D, and the increase in cell killing when the energy of a beam of electrons is increased sufficiently to just penetrate to the cell’s nucleus (see Elkind, 1985, and citations therein). In addition, there is evidence from microorganisms that the genotype of a cell significantly influences radiation response even when the survival curve is exponential (i.e., when a single-hit in the sensitive target is presumed to be sufficient for inactivation; see Elkind, 1977, 1987). Examples are the varying sensitivities of the E. coli K12 isogenic repair mutants (Yatagai and Matsuyama, 1977; Peak et al., 1980), and the genetically controlled repair of radiation damage in yeasts (e.g., Saeki et al., 1980; Reddy and Rao, 1981). Added to observations such as the foregoing is the inference that because genomic DNA has a central biological role, as well as a large target size, it can magnify discrete molecular damage into a lethal effect. This point can be simply illustrated by noting that a cell destined to die (i.e., to lose its ability to yield a clone of cells of unlimited size) may undergo 4–5 divisions before further division ceases and cell lysis becomes apparent (Elkind et al., 1963). During this abortive clonal growth, active DNA, RNA, and protein synthesis takes place as well as active general cell metabolism. The enzymatic and metabolic machinery for these processes represent small targets of which there are multiple copies compared to genomic DNA.

Keywords

Survival Curve Chinese Hamster Ovary Cell Ataxia Telangiectasia Chinese Hamster Cell Shoulder Width 
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Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • M. M. Elkind
    • 1
    • 2
  • H. Utsumi
    • 2
    • 3
  • M. Hagan
    • 4
  • E. Ben-Hur
    • 2
    • 5
  1. 1.Cellular and Molecular Biology Interdisciplinary Program Graduate FacultyColorado State UniversityFort CollinsUSA
  2. 2.Department of Radiology and Radiation BiologyColorado State UniversityFort CollinsUSA
  3. 3.Radiation Biology CenterKyoto UniversityKyoto 606Japan
  4. 4.Baylor College of MedicineHoustonUSA
  5. 5.Nuclear Research Center-NegevBeer-ShevaIsrael

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