Studies on the Combined Effect of Actinomycin D and X-Radiation

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Abstract
Experi-ments were conducted to determine whether the combined effect of actinomycin D and X-radiation is quantitatively greater than the theoretical sum of the effects produced by the same doses of each agent alone, as determined by the single agent response curve (for a given combination of dosage fractions). Potentiation is said to be present when 1/2 dose A of an agent P + 1/ 2 dose B of an agent Q produces an effect greater than X, provided X is the effect of dose A of P and also dose B of agent Q. This definition would apply also to any other combination of fractions of doses of agents P and Q whose sum is unity or less and whose effect is X or more. Potentiation according to the above definition was not demonstrated, as measured by cell or animal death in tissue cultures, mice, or rats. It seems that a different mechanism of toxicity operates in each agent and that the varying degrees of ad-ditivity observed are due merely to a numerical and biological alteration of the cell population by the agent first administered. When small doses of actinomycin D, which in themselves would not markedly alter the cell population were used, additivity withX-rays could not be shown. It appears that, when enhancement of the combined effect occurs, it is only under conditions whereby each agent can effectively decrease the cell population. It can also be stated that the response curve for given increments of X-ray dose is less in the presence of actinomycin D.