Effects of alpha-difluoromethylornithine-induced polyamine depletion on the radiosensitivity of a human colon carcinoma cell line.
The effect of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) on the in vitro radiation response of Clone A human colon adenocarcinoma cells was investigated. Analysis of intracellular polyamine levels showed that exposure of Clone A cells to 1 mM DFMO for 96 h reduced putrescine and spermidine to nondetectable levels, while spermine was decreased by approximately 50%. This DFMO treatment protocol enhanced the radiosensitivity of Clone A cells, which was reflected by a decrease in both the Do and Dq. The addition of putrescine (1 mM) for the final 48 h of DFMO exposure restored polyamine levels and returned clone A radiosensitivity to that of control cells. These results indicate that polyamine depletion by DFMO sensitizes Clone A tumor cells to ionizing radiation.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002588:Cesium Radioisotopes; D003110:Colonic Neoplasms / Q000473:pathology; D000518:Eflornithine / Q000494:pharmacology*; D005720:Gamma Rays; D006801:Humans; D011073:Polyamines / Q000096:biosynthesis*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects
D002588:Cesium Radioisotopes; D011073:Polyamines; D000518:Eflornithine