Effects of nucleoside analogs and sodium butyrate on recovery from potentially lethal X ray damage in human colon tumor cells

Int J Radiat Oncol Biol Phys. 1987 Apr;13(4):593-601. doi: 10.1016/0360-3016(87)90077-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / radiotherapy*
  • Antineoplastic Agents / pharmacology*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology*
  • Butyrates / pharmacology*
  • Butyric Acid
  • Cells, Cultured
  • Colon / radiation effects
  • Colonic Neoplasms / radiotherapy*
  • Decitabine
  • Humans
  • Radiation-Sensitizing Agents*

Substances

  • Antineoplastic Agents
  • Butyrates
  • Radiation-Sensitizing Agents
  • Butyric Acid
  • Decitabine
  • Azacitidine