Changes in the Survival Curve Shape ofE. ColiCells Following Irradiation in the Presence of Uncouplers of Oxidative Phosphorylation

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Abstract
Four uncouplers of oxidative phosphorylation (UOP) (carbonyl cyanide m-chlorophenylhydrazone, 2,4-dinitrophenol, 4-hydroxybenzylidenemalonitrile and N-phenylanthranilic acid) have been found to alter the shape of the radiation survival curves of several cell lines of E. coli when present during irradiation in oxia. Incubation of cells with high concentrations of UOP for 30 min before irradiation induced an increase in extrapolation number (n) in cell lines AB 1157(wild-type), AB 1886(uvrA−) and KMBL(polA−) but not GR 501(lig−)ts, AB 2463(recA−) and AB 2480(uvrA− recA−). In addition the UOP all effect a decrease in mean lethal dose (D0) even when tested at low concentrations or short contact times. Studies with wild-type cells correlate the increase in n with measured increased levels of ATP (above oxic control cells) produced upon incubation with UOP. The increased levels of ATP most likely arise from the UOP overstimulating glycolysis. The decrease in D0 cannot be associated with any of the repair pathways investigated and it is concluded that the highly lipophilic UOP directly or indirectly potentiate other target(s) to radiation damage as well as DNA under oxic conditions. Treatment of the cells with UOP did not result in the deleterious depletion of energy substrates, loss of non-protein thiols or the production of cytotoxins upon irradiation.