THE U.V.‐X‐RAY SYNERGISM IN ESCHERICHIA COLI B/r‐I. INHIBITION BY THE INCORPORATION OF 5–BROMOURACIL AND BY PURINE STARVATION *

THE JOINT action of ultraviolet light (u.v.) and ionizing radiation has been studied in a number of biological systems. These interaction experiments have revealed the existence of both synergistic and antagonistic effects, as well as instances of no interaction at all (see Haynes, 1964a, for review). Stationary phase cells of E. coli B/r exhibit a synergistic u.v.-X-ray interaction which has the following features: (1) Graded, preliminary U.V. exposure increases the X-ray sensitivity up to a factor of three over that of the control cells which have not been exposed to U.V. (2) Graded preliminary X-ray exposure partially removes the shoulder, but has no effect on the apparent limiting slope of the U.V. survival curve. (3) The total kill for any given pair of X-ray and U.V. exposures is commutative, i.e., it is independent of the order in which they are given, despite the contrast in the kinetics of the interaction. This last point rules out the possibility that the synergism is based on reactions between short-lived products of either radiation. Rather it suggests the failure of a post-irradiation process, such as a reactivation mechanism, that normally repairs the DNA defects produced by radiation. This interpretation is supported by the fact that preliminary U.V. irradiation produces a maximum three-fold increase in X-ray sensitivity, which corresponds to the X-ray sensitivity ratio between B/r and Bs-l, and also that the X-ray sensitizing effect of U.V. saturates out as the U.V. survival curve begins its slow approach to a limiting slope (dose 2 1200 ergs mm-*) (Haynes, 1964a, 1964b). To investigate further the mechanism of the u.v.-X-ray interaction, and to test the hypothesis that it arises from failure of a repair or reactivation process, we have examined the effects on the interaction of incorporation of the pyrimidine analog 5-bromouracil (5-BU) into the DNA (5-BU DNA) of E. coli, and of purine starvation of the cells.