The Action of Caffeine on X-Irradiated HeLa Cells: VI. Damping of the Structured Age-Survival Function

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Postirradiation treatment of synchronous HeLa S3 cultures with 4 mM caffeine until greater than or equal to 32 hr after mitotic collection, following exposure to 220-kV X rays at various times during interphase, severely damps the fluctuations in the age-survival curve. Not only does the dose-survival curve essentially lose its shoulder, as reported previously, but it becomes steeper and displays a virtually age-independent terminal slope (D0 congruent to 0.5 Gy). It becomes multicomponent, at least early in the cycle. The residual structure in the interphase age-survival curve, if any, appears to reflect mainly an age-dependent fluctuation in the size of a subpopulation of cells having marked sensitivity to X rays (D0 congruent to 0.25 Gy), though there might be small residual fluctuations in the size of the shoulder and the slope. Mitotic cells also respond to postirradiation treatment with caffeine; they yield a dose-survival curve whose slope is similar to that of the sensitive subpopulation seen in interphase. These findings indicate that most of the structure in the unperturbed age-survival function derives from repair of potentially lethal radiation damage.