Influence of Intracellular Thiol and Polyamine Levels on Radioprotection by Aminothiols

Abstract

We examined the effect of manipulating the levels of two endogenous radioprotectors, glutathione (GSH) and polyamines, on the ability of exogenous aminothiols to protect Chinese hamster ovary cells from the lethal effects of gamma-radiation. Treatment with 0.5 mmol dm-3 buthionine sulfoximine (BSO) for 24 h depleted GSH levels to < 1% of control and significantly sensitized the cells to irradiation in air. Undepleted control cells were protected by WR-1065 (4 mmol dm-3; 30-min preirradiation treatment at 37 degrees C) by 2.09-fold (range 1.98-2.21) at the 10% survival level, whereas BSO-treated cells were protected by a factor of 1.98 (range 1.95-2.14) at this survival level. Thus, GSH depletion had no significant effect on the radioprotective capacity of WR-1065. Treating cells with 1 mmol dm-3 alpha-difluoromethyl ornithine (DFMO) for 48 h depleted the polyamines putrescine and spermidine to very low levels, while spermine was not significantly depleted. DFMO also sensitized cells to aerobic irradiation. WR-1065 protected DFMO-treated cells by 2.29-fold (range 2.08-2.53), whereas undepleted control cells were protected by 2.09-fold (range 1.98-2.21) at the 10% survival level. Thus, WR-1065 appeared to offset the radiosensitizing effect of the DFMO treatment. Cysteamine, on the other hand, protected control and DFMO-treated cells to the same extent. We also examined the effect of combinations of exogenous thiols on radiosensitivity. Cells were treated with WR-1065 (4 mmol dm-3) for 30 min and then with increasing concentrations of dithiothreitol for 5 min prior to irradiation. The protective effects of these two thiols were simply additive.

Geometrical trans Lipid Isomers: A New Target for Lipidomics

“…With inspiration taken from the lipid peroxidation process extensively studied in liposomes,69 unsaturated lipid vesicles were envisaged as a good biomimetic model for the double‐bond isomerization. Indeed, early reports on the use of glutathione, or other thiol compounds, as an effective protective agent against radiation‐induced lipid peroxidation did not mention the stability of the double‐bond geometry 70. Generally speaking, thiol compounds are still regarded as radioprotective agents against the various types of damage on lipids, DNA, and proteins,71 despite the reported activation of PUFA peroxidation, which forwarded the hypothesis that thiols can be a double‐edged sword in the biological environment 72.…”

Thiols and polyamines in the cytoprotective effect of taurine on carbon tetrachloride-induced hepatotoxicity

“…Both polyamine and GSH have been found to act as protective agents against oxidative stress (16,17) and also possess radioprotective abilities (18). Both have also been found to be endogenous mediators of acute gastroprotection involving gastric mucosal defense (19).…”

Thiyl radicals in biosystems: effects on lipid structures and metabolisms

“…Thiols are known to inhibit lipid peroxidation [10][11][12]. Indeed, no lipid consumption due to oxidative degradation could be detected, whereas the isomerization occurred efficiently in quantitative yield (see fig.…”

“…The repair of radical DNA species shown in equation 1 was mostly investigated in radiation studies of biomolecules [9]. Among others, this reaction provides a rationale for the pharmacological application of thiols as radiation-protecting substances, certainly in sense of repair reactions instead of primary shielding [10][11][12].…”