Inhibition of X-ray-induced DNA strand break repair in polyamine-depleted HeLa cells.
Treatment of HeLa cells with the polyamine biosynthesis inhibitors, alpha-difluoromethylornithine (DFMO) or methylglyoxal bis(guanylhydrazone) (MGBG), results in, depending on the conditions, partial or complete depletion of the cellular polyamines: putrescine, spermidine and spermine. In this compromised state cells exhibited a distinct deficiency in repair of X-ray-induced DNA strand breaks. The half-time for return of normal DNA sedimentation following 1.6 Gy was 9.5 min for untreated control cells and 22, 32 and 50 min for cells treated with MGBG, DFMO + MGBG and DFMO, respectively. Normal repair kinetics were restored to these cells upon a short incubation in media containing all three polyamines. The rapid early phase of repair following higher X-ray doses (16 Gy) was also delayed in polyamine-depleted cells but later repair occurring 1-4 h post-irradiation, representing chromatin reconstitution, was apparently normal.
Snyder
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Merrell Dow Research Institute, Cincinnati, OH 45215.
D004260:DNA Repair; D004273:DNA, Neoplasm / Q000528:radiation effects*; D000518:Eflornithine / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008935:Mitoguazone / Q000494:pharmacology; D011073:Polyamines / Q000096:biosynthesis*; D011700:Putrescine / Q000096:biosynthesis; D013095:Spermidine / Q000096:biosynthesis; D013096:Spermine / Q000096:biosynthesis
D004273:DNA, Neoplasm; D011073:Polyamines; D013096:Spermine; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine