Protection against X-irradiation by Sulphydryl Compounds

Abstract

The radioprotective effect of eight thiol compounds with pK-values of their thiol groups varying from 8'5-10'8 was tested on isolated cells in vitro. The influence of variations in pH of the incubation medium between 6-3 and 83 was investigated. The ability of the cells to form colonies was used as the criterion for survival.By comparing the protection affected by different concentrations of the various compounds it was found that a good correlation existed between the degree of radio-protection and the thiolate concentration in the medium. This correlation was also found to be present under anoxic conditions. It was concluded that the increase of the radio-protective activity of the thiol compounds, caused by an increase of either concentration, pH or temperature, can be explained by an increase of the amount of thiol compound present inside the cell. The differences in radio-protective activity of the various compounds cannot be explained by differences in cellular uptake.The thiol compounds with a pK-value lower than 10 appeared to be very toxic at concentrations between 01 and 2-0 mM, but not at concentrations lower than 0-1 mM and between 2 to c. 100 mM. This striking toxicity could be prevented by incubation under anoxic conditions, by a decrease of the pH to 63, by addition of an excess of another thiol compound or of KCN, but not by addition of NaS,0 3 . The toxic action of the thiol compounds at these concentrations seems to be caused by an irreversible intracellular reaction of a specific oxidation product of these compounds with some cellular constituant.

Radioprotective stereostructure-activity study of cis- and trans-2-mercaptocyclobutylamine analogs and homologs of 2-mercaptoethylamine

“…Unless these analogs are taken into the cell by some stereoselective process these data argue against the proposal that the degree of radioprotection is only dependent upon the intracellular thiolate ion concentration. 52 The greater activity of trans-2, -3, and -4 (5 mM concentration) over MEA (1) might be due to increased thiolate ion concentration owing to increased absorption of the more lipophilic cyclobutanes. However, trans-2 and -4 have significantly different radioprotective activities (Table III) but similar pKa's and predicted lipid solubilities.…”

γ-Radiolysis of disulfides in aqueous solution. III. L-Cysteine-D-penicillamine mixed disulfide

“…O H radicals and oxygen (as 0-,) this may be one of the important properties which determines whether or not a compound is radio-protective. In this connection it is interesting to note that Vos et al (5) found that penicillamine protected cells almost as well as cysteine under anoxic conditions (i.e. in the absence of 0-,).…”

“…Reactions [l] and [2] seem to occur with both cystine and penicillamine disulfide although reaction [XI may be more important than [ I ] in the case of penicillamine disulfide. Reactions [3], [4], and [5] probably occur with both CySOH and PenSOH and reaction [5] could be one of the reactions leading to the symmetrical disulfides. Reaction [6] is more specific as it does not occur with PenSOH.…”

Chemoprotective effect of cysteamine against the induction of micronuclei by methyl methanesulfonate and cyclophosphamide

“…Takagy et al (1974), in experiments conducted on Hela cells observed that the genotoxicity of MEA at low concentrations developed gradually over time during which hydrogen peroxide was generated in the medium, with the addition of catalase and peroxidase inhibiting this "paradoxical" effect. Vergroesen et al (1967), demonstrated that thiols with a pK value of less than 10 were toxic at concentrations of 0.1 and 2.0 mM, with the addition of another thiol at high concentrations, the lowering of the pH or the presence of KCN (which has no radioprotective power and has no effect on the radioprotective action of SH compounds), eliminating the toxicity. Whereas the addition of Na 2 S 2 O 3 (which does not penetrate the cell) to the system does not change the toxic condition, a fact probably indicating that this toxicity may be due to a process occurring at the intracellular level, possibly of an oxidative nature.…”

“…MEA can protect mammalian cells from radiologic phenomena such as cell death (Barendsen, 1964;Eker and Pihl, 1964;Vergroesen et al, 1967;Sinclair, 1967;1968;Vos, 1969), mitotic delay (Firket and Mathieu, 1966), chromosome aberrations (Yang and Hahn, 1968;Vos and Kaalen, 1968) and depression of DNA synthesis (Honjo, 1963). Santos-Mello (1977) reported that MEA can also inhibit DNA repair (unscheduled DNA synthesis -UDS) as well as the repair of radioinduced chromosome breaks in human lymphocytes.…”