Effects of Polyamines and Thiols on the Radiation Sensitivity of Bacterial Transforming DNA

Abstract

The effects of polyamines on the loss of biological activity of bacterial transforming DNA irradiated in the absence and presence of sulphydryl-containing compounds has been investigated. In both oxygenated and hypoxic conditions the polyamines (spermine, spermidine, putrescine and cadaverine) are radioprotectors with the degree of protection increasing with increasing polyamine concentration. When O2-saturated DNA solutions are irradiated, the degree of radioprotection by polyamines generally correlates with the efficiency of scavenging of OH. radicals. In N2 the protection does not show that correlation; several possible reasons are discussed. With the exception of spermine, the polyamines are slightly more protective of oxygenated DNA than of hypoxic DNA. When DNA is irradiated in the presence of both polyamines and thiols, the combined protection is usually greater than that exhibited by either agent alone. When irradiation is in oxygen, the combined agents appear to operate by the same mechanism, namely OH. radical scavenging. In N2-saturated solutions, polyamines and dithiothreitol appear to act by different, non-interacting mechanisms; however WR1065 and polyamines may radioprotect by the same mechanism. Also, the results suggest that polyamines may reduce the ability of some thiols to radioprotect DNA.

Effects of Trypanothione on the Biological Activity of Irradiated Transforming DNA

“…ments), the difference in repair rates becomes greater . This is consistent with the observation of Held and Awad (1991) that in the t-DNA system sodium chloride at high concentrations decreased the amount of radioprotection of transforming DNA by spermidine .…”

“…This suggests that the presence of the positive charge on the polyamine portion of trypanothione may allow trypanothione to become more concentrated near DNA than predicted by the net overall charge of the molecule . Held and Awad 1991) also showed that when DTT (10 µmol dm -) was combined with 1 mmol dm -3 spermidine the protection factor in N 2 was 6 .8, and the data were consistent with the explanation that DTT and spermidine were acting by independent non-interacting mechanisms . The concentration of spermidine alone used in the experiments reported here is not high enough to show any radioprotection .…”

“…Reduced glutathione, with a -1 net charge, shows a protection factor for t-DNA of 2 .5 at lopmol dm -3 GSH (5 µmol dm -3 GSSG, Table 1), whereas reduced trypanothione, with a + 1 net charge, shows a protection factor of 9 .8 at the same concentration . The results of the present work can be compared to those of Held and Awad (1991) where polyamines were combined with thiols in similar experiments, and by Held et al . (1984a) comparing protection of t-DNA by various thiols .…”

Protecting or promoting effects of spermine on DNA strand breakage induced by iron or copper ions as a function of metal concentration

“…It is generally believed that electrostatic interactions of polyamines with different polyanions, especially nucleic acids, could explain their effects on protein synthesis, chromatin structure and gene expression [17], although the implication of structural specificity for each polyamine cannot be ruled out. Different in vitro studies have clearly shown that spermine exerts a marked protective effect against DNA damage induced by endoperoxides [18,19], ionizing radiation [20,21], fast neutrons [22] or Cu(II)/H 2 O 2 [9,23]. Several mechanisms have been proposed to explain this protection: compaction of DNA structure by spermine that would reduce the accessibility of DNA to the reactive species [21,22], direct scavenging of ROS by spermine [22,23] and the formation of chelates with the metal, which may prevent the generation of the highly reactive species [24].…”

Naturally Occurring SLE Anti‐DNA Antibodies Recognize Unique Conformation on DNA‐Lysine Photoadduct

“…These compounds include polyamines, histones and nuclear matrix elements. Polybasic molecules found in the cells have great affinity for acidic constituents such as DNA (6) and their interaction might play a role in the pathogenesis of SLE.…”