Effect of uncouplers of oxidative phosphorylation (UOP) on the radiosensitization of E. coli after a short contact time

UOP were added just prior to irradiation to decrease the proton gradient (μ/sub H/+) by destroying the chemical gradient (ΔpH). Serially dosed samples were washed free of UOP. The concentration efficiencies of the UOP (CCCP >4-hydroxybenzyl-idenemalonitrile >N-phenylanthranitrilic acid) in effecting increases in n and decreases in D/sub o/ under aerobic conditions correlates well with their abilities to uncouple. Similar effects were found for the DNA repair deficient strains AB2463 (recA/sup -/), Ab1886(uvrA/sup -/), AB2480(recA/sup -/) and KMBL (polA/sup -/) implying that a decreased μ/sub H/+ does not influence these repair pathways. Strain GR 501ts (lig/sup -/) deviated from this pattern by not increasing n. As ligase activity is essential for DNA synthesis (and in certain DNA repair pathways) it might well be that its absence permits essential repair processes to be completed before a form of mis-repair perhaps involving DNA synthesis occurs. Since UOP effect a decrease in D/sub o/ in all cell lines it is unlikely to be associated with an enzymatic repair of DNA but with some fast chemical repair. Experiments with dinitrophenol, a UOP possessing a moderate electron-affinity (E) and radical pK <7, showed that unlike UOP at low E and radical pK/sub a/ >7, it sensitized hypoxic wildtype cells as well