Effects of some Metabolic Inhibitors on X-ray Dose-response Curves for the Survival of Mammalian Cellsin vitro, and on Early Recovery between Fractionated X-ray Doses

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Abstract
The rapid (0-8 hr.) recovery from sub-lethal X-ray damage in HeLa S-30Xf cells in vitro is neither delayed nor reduced in magnitude by incubating the cells in media containing high concentrations of 2-4 dinitrophenol [DNP], which deprives the cells of a major energy source by uncoupling oxidative phosphorylation. Cells surviving 100 [mu]g/vil concentrations of DNP showed somewhat increased recovery between fractionated X-ray doses. 5-fluorouracil in high concentrations sensitises the cells to single X-ray exposures, but the steeper dose-response curve retains a marked shoulder and no significant modification of the two-dose recovery curve is seen even with drug concentrations that are high enough to reduce cell survival drastically on their own. The antibiotics puromycin and cycloheximide, although inhibiting protein synthesis and sensitizing cells to the effects of single doses of X-rays, do not decrease early recovery even when the drug under study is added to the cell cultures as much as 20 hr. prior to the 1st X-ray dose. The folic acid antagonist methotrexate, when added to the growth medium, sensitizes cells to the effects of single doses of X-rays, producing an almost shoulderless survival curve. No measurable recovery is observed when fractionated doses of X-rays are delivered at times greater than 16 hours after addition of the drug to the medium. The possible inferences to be drawn from these results for combined courses of radiotherapy and chemotherapy are discussed.