Abstract
In classical theories of radiobiological action, cell killing is viewed as an inevitable consequence of the accumulation of some given number of physical "hits" in sensitive, intracellular targets. Shoulders on survival curves are attributed to the need for more than one hit to produce the observed effect, and to the random distribution of these hits among the cells in an irradiated population. Such curves start with zero slope at very low doses, and, at high doses, they approach, asymptotically, exponential slopes that are inversely proportional to the dose required for one hit, or to inactivate a single target. Unfortunately, these simple ideas provide no credible explanation for the dramatic changes in apparent final slope, and the total abolition of shoulders, that are observed in many radiation-sensitive mutants. The damage-repair hypothesis asserts that the surviving fraction of cells in a mutagen-treated population is proportional to the number of potentially lethal lesions that are not removed by any repair process. Evidence indicates that these repairable lesions are located in DNA; however, this fact is irrelevant to the mathematical development of dose-response equations under the damage-repair hypothesis. The survival curves for repair-proficient cells generally exhibit a shoulder which reflects a decline in the efficiency of repair with increasing dose. Introduction of the concepts of "error-prone" and "recombinagenic" repair allows the extension of these ideas to data on induced mutation and mitotic recombination.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BENDER M. A., GOOCH P. C. The kinetics of x-ray survival of mammalian cells in vitro. Int J Radiat Biol Relat Stud Phys Chem Med. 1962 May;5:133–145. doi: 10.1080/09553006214550651. [DOI] [PubMed] [Google Scholar]
- Blakely E. A., Tobias C. A., Yang T. C., Smith K. C., Lyman J. T. Inactivation of human kidney cells by high-energy monoenergetic heavy-ion beams. Radiat Res. 1979 Oct;80(1):122–160. [PubMed] [Google Scholar]
- Brendel M., Haynes R. H. Interactions among genes controlling sensitivity to radiation and alkylation in yeast. Mol Gen Genet. 1973 Sep 12;125(3):197–216. doi: 10.1007/BF00270743. [DOI] [PubMed] [Google Scholar]
- Eckardt F., Haynes R. H. Kinetics of mutation induction by ultraviolet light in excision-deficient yeast. Genetics. 1977 Feb;85(2):225–247. doi: 10.1093/genetics/85.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eckardt F., Haynes R. H. Quantitative measures of mutagenicity and mutability based on mutant yield data. Mutat Res. 1980 Dec;74(6):439–458. doi: 10.1016/0165-1161(80)90175-2. [DOI] [PubMed] [Google Scholar]
- Hanawalt P. C., Cooper P. K., Ganesan A. K., Smith C. A. DNA repair in bacteria and mammalian cells. Annu Rev Biochem. 1979;48:783–836. doi: 10.1146/annurev.bi.48.070179.004031. [DOI] [PubMed] [Google Scholar]
- Kunz B. A. Genetic effects of deoxyribonucleotide pool imbalances. Environ Mutagen. 1982;4(6):695–725. doi: 10.1002/em.2860040609. [DOI] [PubMed] [Google Scholar]
- Kunz B. A., Haynes R. H. Phenomenology and genetic control of mitotic recombination in yeast. Annu Rev Genet. 1981;15:57–89. doi: 10.1146/annurev.ge.15.120181.000421. [DOI] [PubMed] [Google Scholar]
- Wheatcroft R., Cox B. S., Haynes R. H. Repair of UV-induced DNA damage and survival in yeast. I. Dimer excision. Mutat Res. 1975 Nov;30(2):209–218. [PubMed] [Google Scholar]
- Witkin E. M. Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol Rev. 1976 Dec;40(4):869–907. doi: 10.1128/br.40.4.869-907.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]