Radiation Protection of Tissue Culture Cells by Anoxia, Cysteamine and a Combination of Anoxia and Cysteamine

Vergroesen, A.J.; Vos, O.; Budke, L.

doi:10.1038/194100a0

Cited by 17 publications

(7 citation statements)

References 5 publications

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“…Hence the DRF's obtained by this method for protective compounds will not necessarily be the same a s those obtained by the cell clone techniques. In fact they appear t o be considerably higher, although the effect of anoxia (DKF = 2.1) is comparable t o the value obtained by clone techniques (1,27). I t is of interest t h a t the DKF's obtained for anoxia by scoring chromosome abnormalities are appreciably higher than 2 (26,28).…”

Section: Discussionmentioning

confidence: 56%

The Ehrlich Ascites Carcinoma as a Tool for the Rapid Evaluation of the Efficacy of Radioprotective Compounds at the Cellular Level

Jf¹

1964

Can. J. Biochem.

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A simple, rapid quantitative method for biologically evaluating radioprotective compounds a t the cellular level has been developed by ineans of Ehrlich mouse ascites tumor cells. The cells were irradiated in vitro and subsequently grown in vivo and the radioprotective compound was evaluated by its ability to prevent mitotic arrest and loss of proliferative capacity in the cells. Results statistically significant a t the 1% level were available in 48 hours when groups of 15 mice per sample were compared. L-Cysteine was found to be a better protector than 2-an~inoethylisothiouronium bromide hydrobomide or 2-mercaptoethylamine and also increased the protection of cells irradiated under anaerobic conditions.

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Section: Discussionmentioning

confidence: 56%

The Ehrlich Ascites Carcinoma as a Tool for the Rapid Evaluation of the Efficacy of Radioprotective Compounds at the Cellular Level

Jf¹

1964

Can. J. Biochem.

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“…Since these experiments were performed on animals and all the sulphydryl compounds produce pronounced pharmacological and toxic effects, the interpretation of these data at the cellular level is very difficult. They emphasized that these rising intracellular sulphydryl levels were closely related to the increasing radioprotection as observed by Vos, Budke and Vergroesen (1962) with mammalian cells in tissue culture. Bacq 1965).…”

Section: Introductionmentioning

confidence: 75%

“…For the experiments involving anoxia, nitrogen was flushed over the cells according to a technique described by Vergroesen, Budke and Vos (1963). For the experiments involving anoxia, nitrogen was flushed over the cells according to a technique described by Vergroesen, Budke and Vos (1963).…”

Section: Methodsmentioning

confidence: 99%

“…The search for more potent or less toxic radio-protective agents is further complicated by the lack of knowledge about the mode of action of these compounds (cf. To explain this phenomenon Vergroesen, Budke and Cohen (1964) postulated that the radioprotective action of the thiol compounds is exercised by the dissociated form of the -SH-groups and thus depends on the thiolate concentration in the cellular environment. Finally, little is known about their distribution in the intracellular compartments.…”

Section: Introductionmentioning

confidence: 99%

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Protection against X-irradiation by Sulphydryl Compounds

Vergroesen

Budke

Vos

1967

International Journal of Radiation Biology and Related Studies

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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.

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“…It has been shown with yeast (Wood 1959), with bacteria (Kohn and Gunter 1960), and with human cells in tissue culture (Vergroesen, Vos and Budke 1962), that the protective action of the sulphydryl compounds, of which AET is an example, does not depend on removal of oxygen alone. While the results of those experiments have important implications concerning the basic mechanism of action of the sulphydryl compounds, they do not necessarily indicate that therapeutic synergism will result when the sulphydryl compounds are combined with hypoxia, as the experiments did not include all the factors of the therapeutic situation in the intact animal.…”

Section: Discussionmentioning

confidence: 95%