Potentiation of X ray sensitivity by combinations of sodium butyrate and buthionine sulfoximine.
The ability of various concentrations of the differentiation-inducing agent sodium butyrate (NAB, 0-2 mM) to produce radiosensitization in human colon tumor cells when combined with varying concentrations of the irreversible inhibitor of gamma-glutamyl cysteine synthetase, buthionine sulfoximine (BSO, 0-0.75 mM) was studied. We have previously shown that high concentrations of each agent in combination (2 mM NAB + 0.5 mM BSO) produced a supra-additive effect in terms of radiosensitization as indicated by a decrease in the quasi-threshold value (Dq) of the single dose survival curve; we wished to define responses at other concentrations. Cells were adapted in vitro to growth in medium containing NAB for 3 passages prior to x-irradiation and BSO was given acutely 24 hrs before the x-irradiations. The most effective combination was 0.3 mM NAB + 0.75 mM BSO. These data suggest that adaptation of tumor cells to chronic low levels of a differentiation-inducing agent such as NAB followed by administration of BSO just prior to irradiation might be an effective combination in producing increased response of solid tumors.
Leith
J T
JT
Radiation Biology Laboratories, Brown University, Providence, RI.
D019328:Buthionine Sulfoximine; D002087:Butyrates / Q000008:administration & dosage*; D020148:Butyric Acid; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D003131:Combined Modality Therapy; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D008717:Methionine Sulfoximine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D002087:Butyrates; D011838:Radiation-Sensitizing Agents; D020148:Butyric Acid; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine