Effects of nucleoside analogs and sodium butyrate on recovery from potentially lethal X ray damage in human colon tumor cells.
The effects of 5-azacytidine (5-aza-CR) and 5-aza-2'-deoxycytidine (5-aza-CdR) both alone and in combination with sodium butyrate (NaB) on intrinsic radiation sensitivity and ability to recover from potentially lethal damage (PLDR) were studied in two subpopulations of cells (clones A and D) from a heterogeneous human colon adenocarcinoma (DLD-1). Growth for three passages in medium containing 1 mM NaB alone enhanced radiation cell killing in the low dose ("shoulder") region of the survival curve for both cell lines. Neither 1.0 microM 5-aza-CR nor 0.25 microM 5-aza-CdR alone enhanced cell killing. However, treatment of these cells with a combination of either 5-aza-CR or 5-aza-CdR and NaB enhanced radiation cell killing at a clinically relevant dose level of 2.0 Gy by approximately 25% for both clone A and clone D cells. Also, while exposure to these differentiation-inducing agents separately enhanced the expression of PLDR in both tumor subpopulations, treatment with either of the combinations reversed this increase in PLDR. These results indicate that the gene-activating agents 5-aza-CR, 5-aza-CdR, and NaB may interact to modify the radiation sensitivity of two human tumor cell lines. Such combinations may prove useful clinically, if enhanced X ray cell killing of tumor cells can be achieved without a concomitant enhancement of recovery from potentially lethal X ray damage.
D000230:Adenocarcinoma / Q000532:radiotherapy*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002478:Cells, Cultured; D003106:Colon / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D000077209:Decitabine; D006801:Humans; D011838:Radiation-Sensitizing Agents
D000970:Antineoplastic Agents; D002087:Butyrates; D011838:Radiation-Sensitizing Agents; D020148:Butyric Acid; D000077209:Decitabine; D001374:Azacitidine