Mechanism of the radioprotecting action of chemical compounds on Escherichia coli cells

Abstract

The effect of radioprotection of indolylalkylamines (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 carrying plasmids (ColE1). This procedure enabled to determine the in vivo rate of enzymatic incision of gamma-sites. It was found that the protectors did not change the total amount of gamma-damages in DNA but reduced the rate of enzymatic incision.

Usefulness of the SOS Chromotest in the study of medicinal plants as radioprotectors

“…The electrostatic binding to and stabilization of the DNA molecule by the thiol and disulfide forms of amifostine may facilitate a more efficient repair of DNA damage post-irradiation. In this sense, it is known in E. coli that strains deficient in different repair mechanisms of ionizing radiation-induced damage were not protected by aminothiols, suggesting that the protection may involve an increase in repair (Bresler et al 1978, Hü lsewede & Schulte-Frohlinde 1986. Likewise, enhanced post-replication repair and recombination mechanisms have been observed after treatment of E. coli cells with antimutagenic compounds (Ohta et al 1988), suggesting that both excision repair and recombination repair are necessary for protection.…”

Amifostine Metabolite WR-1065 Disrupts Homologous Recombination in Mammalian Cells

“…RecA − ) (40). Similar studies in S. cerevisiae confirmed this observation using HR-deficient rad − yeast mutants.…”

Chemical protection against ionizing radiation. Final report

“…The yield and nature of radical and molecular species formed on irradia tion of water is influenced to a great degree by the presence-of molecular oxygen (reviewed by [78]). Molecular oxygen has a high affinity for the reducing radicals H' and e" a q, forming perhydroxyl The reactions between organic compounds and the primary products of water radiolysis have been studied extensively.…”

“…Oespite long-standing research attention to radioprotection through prevention of DNA injury, some radioprotective agents act in part, at least, through the enhancement of repair processes rather than by the prevention of DNA lesions. Indeed, work with repair-deficient mutant bacteria led Bresler [78] to postulate that repair enhancement is the main mechanism of radioprotectant action.…”