Enhancement of Radiation Killing of Cultured Mammalian Cells by Cordycepin

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Abstract
Asynchronous populations of rat hepatoma cells (H4) in log-phase growth survived a 3-hour exposure to cordycepin (3′-deoxyadenosine), an RNA antimetabolite, in a simple exponential fashion with a ‘D0’ of 43·8 μM/l. When cordycepin-treated cells were exposed to X-irradiation, the resultant survival levels were much lower than one would expect were the agents simply additive. Patterns of X-ray survival of cells treated with cordycepin were dependent on drug concentration, the predominant effect being to decrease the D0 of the X-ray survival curve. The increased sensitivity of cells exposed to cordycepin to subsequent X-ray treatment persists for longer than 4 hours after drug administration. Although immediate cordycepin post-treatment of X-irradiated cells is less effective than pre-treatment, the interaction is still significant. Cordycepin treatment did not appear to reduce split-dose recovery or to inhibit the rejoining of single-strand breaks as measured by DNA sedimentation in alkaline-sucrose gradients.