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Related Experiment Videos

Radiosensitization by diamide analogs and arsenicals.

E A Bump, G P Jacobs, W W Lee

    International Journal of Radiation Oncology, Biology, Physics
    |August 1, 1986
    PubMed
    Summary

    Glutathione (GSH) oxidizing reagents like SR-4077 enhance cell radiosensitivity by depleting cellular thiols. This radiosensitization, particularly affecting the shoulder of survival curves, suggests a role for protein thiols in DNA repair after X-ray exposure.

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    Area of Science:

    • Cellular and Molecular Radiobiology
    • Biochemistry

    Background:

    • Glutathione (GSH) is a key cellular reducing agent involved in protecting cells from oxidative stress.
    • Diamide and its analogs are reagents that oxidize GSH, potentially impacting cellular radiosensitivity.

    Purpose of the Study:

    • To investigate the radiosensitizing potential of diamide analogs, focusing on SR-4077.
    • To elucidate the mechanism by which GSH oxidizing reagents sensitize aerobic cells to X-ray irradiation.

    Main Methods:

    • Testing of several diamide analogs as radiosensitizers in aerobic cells.
    • Assessment of SR-4077's radiosensitizing effects on Chinese Hamster Ovary (CHO) cells, including post-irradiation drug addition.
    • Evaluation of phenylarsine oxide's effect on cell survival curves.

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    Main Results:

    • Radiosensitization generally correlated with the rate of reaction with cellular reducing agents, occurring when cellular reductive capacity was exceeded.
    • SR-4077 demonstrated radiosensitizing effects on aerobic CHO cells, altering both the slope and shoulder of the radiation cell survival curve.
    • Phenylarsine oxide also sensitized aerobic CHO cells, specifically modifying the shoulder of the survival curve.

    Conclusions:

    • The findings support the hypothesis that GSH oxidizing agents sensitize cells by depleting protein thiols.
    • These protein thiols are likely involved in the repair of X-ray-induced DNA damage, explaining the observed radiosensitization.
    • SR-4077 is a valuable tool for mechanistic studies due to its efficacy and reduced cytotoxicity compared to diamide.