Summary
The effect of radioprotection of indolylakylamines (5-methoxytryptamine) and aminothiols (cysteamine) on E. coli cells is practically absent if the cells have genetic defects in the repair systems. This means that the explanation of radioprotection by scavenging of free radicals is invalid and that specific repair mechanisms may be involved. In order to explain the radioprotective mechanism it was suggested that the radioprotectors interact with the damaged sites in DNA so that they become partly screened from repairing endonucleases. Under these conditions the reduction of incision rate results in diminished enzymatic induction of lethal double-strand breaks in DNA, this being important only in wild type cells.
To prove this hypothesis an experimental procedure was developed using bacterial cells carryng plasmids (ColE1). This procedure enabled to determine the in vivo rate of enzymatic incision of γ-sites. It was found that the protectors did not change the total amount of γ-damages in DNA but reduced the rate of enzymatic incision.
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Blair, D.G., Clewell, D.B., Sheratt, D.Y., Helinski, D.R.: Strand-specific supercoiled DNA-protein relaxation complexes; comparison of the complexes of bacterial plasmids ColE1 and ColE2. Proc. nat. Acad. Sci. (Wash.) 68, 210–214 (1971)
Bonura, T., Smith, K.C., Kaplan, H.C.: Enzymatic induction of DNA double-strand breaks in γ-irradiated E. coli K-12. Proc. nat. Acad. Sci. (Wash.) 72, 4265–4269 (1975)
Bresler, S.E.: Theory of misrepair mutagenesis. Mutation Res. 29, 467–472 (1975c)
Bresler, S.E., Noskin, L.A., Agamalyan, E.G., Kuzovleva, N.A.: Role of vegetative and repair DNA synthesis in the elimination of single-strand breaks induced by gamma-irradiation in Escherichia coli. Genetics [in Russian] II, 10, 79–89 (1975a)
Bresler, S.E., Noskin, L.A., Sverdlov, A.G., Stepanova, I.M.: Selective activation of DNA repair synthesis by indolylalkylamines and its role in radioprotector effect of these compounds in Escherichia coli. Proc. Acad. Sci. USSR [in Russian] 219, 4, 985–987 (1974)
Bresler, S.E., Noskin, L.A., Sverdlov, A.G., Stepanova, I.M., Narizhni, S.N.: Genetic determination of the radioprotective action of cysteamine on γ-irradiated E. coli cells. Radiobiol. [in Russian] 16, 6, 824 (1976)
Bresler, S.E., Sverdlov, A.G., Noskin, L.A., Stepanova, I.M.: Influence of genotype of bacterial cells on radioprotective action of indolylalkylamines. Studia biophys 53, 163–166 (1975b)
Carrier, W.L., Setlow, R.B.: Endonuclease from Micrococcus luteus wich has activity toward ultraviolet-irradiated deoxyribonucleic acid: purification and properties. J. Bact. 102, 1, 178–186 (1970)
Cerutti, P.A.: Repairable damage in DNA: Overview. In: Molec. mechanisms for repair of DNA (P.S. Hanawalt, R.B. Setlow, eds.), pp. 3–12. New York-London: Plenum Press 1975
Clewell, D.B., Helinski, D.R.: Supercoiled circular DNA protein complex in Escherichia coli: purification and induced conversion to an open circular DNA form. Proc. nat. Acad. Sci. (Wash.) 62, 1159–1166 (1969)
Dalrymple, G.V., Baker, M.L., Sanders, J.L., Moss, A.J., Nash, J., Wilkinson, K.p.: Do mammalian cells repair radiation injury by the “Cut-and-Patch” mechanism? II. An extension of the original model. J. theor. Biol. 28, 121–142 (1970)
Dertinger, H., Jung, H.: Molecular radiation biology. Berlin-Heidelberg-New York: Springer 1970
Domon, M., Barton, B., Porte, A., Raut, A.M.: The interaction of caffein with ultraviolet light-irradiated DNA. Int. J. Radiat. Biol. 17, 4, 395–398 (1970)
Friedberg, E.C., Goldthwait, D.A.: Endonuclease II of E. coli. Isolation and purification. Proc. nat. Acad. Sci. (Wash.) 62, 3 934–940 (1969)
Ginsberg, D.M., Webster, H.K.: Chemical protection against single-strand breaks in DNA of gamma-irradiated E. coli. Radiat. Res. 39, 421–435 (1969)
Gottesman, M.M., Hicks, M.L., Gellert, M.: Genetics and function of DNA ligase in Escherichia coli. J. molec. Biol. 77, 4, 531–547 (1973)
Hotz, G., Mauser, R.: Infectious DNA from Coli phage TI. II. Host cell reactivation of UV-irradiated molecules. Molec. gen. Genet. 108, 233–242 (1970)
Humphreys, G.D., Willshaw, G.A., Anderson, E.S.: A simple method for the preparation of large quantities of pure plasmid DNA: Biochim. biophys. Acta (Amst.) 383, 457–463 (1975)
Johansen, I., Howard-Flanders, P.: Macromolecular repair and free scavenging in the protection of bacterical against x-rays. Radiat. Res. 24, 184–200 (1965)
Kaplan, H.: DNA strand scission and loss of viability after x-irradiation of bacterial cells. Proceedings of the Third Inter. Congress of Radiat. Res. held at Cortina d'Ampezzo Italy, 1966 (Silini, ed.). Amsterdam: North-Holland Publishing Company 1967
Kavenoff, R., Zimm, B.H.: Chromosome-sized DNA molecules from Drosophila. Chromosoma (Berl.) 41, 1–27 (1973)
Kondakova, N.V., Levitman, M.Kh., Tselikova, S.V., Eidus, L.Kh.: Study in the mecahnisms of radioprotection of DNA. Radiobiol. [in Russian] 15, 4, 506–511 (1975)
Konrad, E.B., Modrich, P., Lehman, R.: Genetic and enzymatic characterization of a conditional lethal mutant of Escherichia coli K-12 with a temperature-sensitive DNA ligase. J. molec. Biol., 77, 519–529 (1973)
Kravetskaya, T., Bagiyan, G.A., Belyakova, N.V., Krutyakov, V.M.: Effect of radioprotectors on endogeneous synthesis and DNA degradation in nuclei and chromatin. Radiobiol. [in Russian] in press (1978)
Kupersztoch-Portnoy, Y.M., Helinski, D.R.: Breaks induced in supercoiled colicinogenic factor E1 DNA as a result of the decay of incorporated tritium. Biochem. biophys. Acta (Amst.) 374, 316–323 (1974)
Lee, C.S., Davidson, N.: Physico-chemical studies on the minicircular DNA in Escherichia coli 15. Biochim. biophys. Acta (Amst.) 204, 285–295 (1970)
Mitzel-Landbeck, L., Schutz, G., Hagen, U.: In vitro repair of radiation-induced strand breaks in DNA. Biochim. biophys. Acta (Amst.) 432, 2, 145–153 (1976)
Moss, A.J., Cleen, J.R., Dalrymple, V., Sanders, J.L., Wilkinson, K.P., Nash, J.C.: Dinitrophenol inhibits the rejoining of radiation-induced DNA breaks by L-cells. Biophys. J. 11, 158–173 (1971)
Okada, Sh.: In Radiation biochemistry, Vol. I: Cells. New-York and London: Academic Press 1970
Pitra, Ch., Hartwig, M., Körner, I.Y., Malz, W.: Radioprotective action of cysteamine: Primary DNA lesions, cell survival and mutation frequency. Studia biophys. (Berl.) 62, 1 31–43 (1977)
So, M., Gill, R., Falkow, S.: The generation of Col E1-Apr cloning vehicle which allows detection of inserted DNA. Molec. gen. Genet. 142, 239–249 (1975)
Strauss, B.S., Robbins, M.: DNA methylated in vitro by monofuctional alkylating agent as a substrate for a specific nuclease from Micrococcus lisodeicticus. Biochim. biophys. Acta (Amst.) 161, 68–75 (1968)
Strniste, G.F., Wallace, S.S.: Endonucleolytic incision of x-irradiated deoxyribonucleic acid by extracts of Escherichia coli. Proc. nat. Acad. Sci. (Wash.) 72, 1997–2001 (1975)
Thomas, M., Davis, R.W.: Studies on the cleavage of bacteriophage Lambda DNA with Eco R1 restriction endonuclease. J. molec. Biol. 91, 3, 315–328 (1975)
Tomilin, N.: On the presence of an endonuclease acting on UV-irradiated and depurinated DNA in Micrococcus lysodeikticus cells. J. molec. Biol. [in Russian], 8, 4, 557–568 (1974)
Tomilin, N., Paveltchuk, E.B., Mosevitskaya, T.: Substrate specificity of the ultraviolet-endonuclease from Micrococcus luteus. Europ. J. Biochem. 69, 265–272 (1976)
Verly, W.G.: Maintenance of DNA and repair of apurinic sites. In: Molec. mechanisms for repair of DNA (P.S. Hanawalt, R.B. Setlow, eds.) New York-London: Plenum Press, Vol. 5, pp. 39–46 1975
Witte, W., Böhme, H.: The action of caffein on the survival of proteus mirabilis and its virulent phage YIr after UV-irradiation and treatment with nitrogen mustard. Mutation Res. 16, 133, 1–6 (1972)
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Bresler, S.E., Noskin, L.A., Stepanova, I.M. et al. Mechanism of the radioprotecting action of chemical compounds on Escherichia coli cells. Molec. Gen. Genet. 163, 75–85 (1978). https://doi.org/10.1007/BF00268966
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DOI: https://doi.org/10.1007/BF00268966