Inhibition of X-Ray-Induced Potentially Lethal Damage (PLD) Repair by Cordycepin (3′-Deoxyadenosine) and Enhancement of Its Action by 2′-Deoxycoformycin in Chinese Hamster hai Cells in the Stationary Phase in Vitro

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Abstract
The effects of growth phase and chemicals on PLD [potentially lethal damage] repair were studied in X-irradiated Chinese hamster hai cells [to develop improvements in cancer therapy by radiation]. The change in capacity of cells in different growth phases to repair PLD was investigated. Starting from cells in the log phase the magnitude of PLD repair during 10 h of postirradiation incubation in Hanks'' balanced salt solution increased from 2.5-18 as the cultures approached the stationary phase on the 7th or 8th day. The effects of chemicals dissolved in Hanks'' BSS [balanced salt solution] on PLD repair were studied using 10th or 12th day cultures. Among the chemicals tested, caffeine and cordycepin were effective in inhibiting PLD repair; the latter was more potent. The time course of cordycepin''s action showed a fall in the surviving fraction followed by a rise, suggesting degradation of the drug. When 2''-deoxycoformycin, an inhibitor of adenosine deaminase, was combined with cordycepin the effect of cordycepin was enhanced. Due to this prevention of the deamination of cordycepin by 2''-deoxycoformycin, the inhibition of PLD repair was prolonged, indicating a possible clinical application of cordycepin as a radiosensitizer.

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