Radiosensitization of GL261 glioma cells by tetraiodothyroacetic acid (tetrac)

Cell Cycle. 2009 Aug 15;8(16):2586-91. doi: 10.4161/cc.8.16.9328. Epub 2009 Aug 22.

Abstract

We studied effects of tetrac (tetraiodothyroacetic acid) on survival of GL261, a murine brain tumor cell line, following single doses of 250 kVp x-rays and on repair of damage (sublethal and potentially lethal damage repair; SLDR, PLDR) in both exponential and plateau phase cells. Cells were exposed to 2 muM tetrac (1 h at 37 degrees C) prior to x-irradiation. At varying times after irradiation, cells were re-plated in medium without tetrac. Two weeks later, colonies were counted and results analyzed using either the linear-quadratic (LQ) or single-hit, multitarget (SHMT) formalisms. Tetrac sensitized both exponential and plateau phase cells to x-irradiation, as shown by a decrease in the quasi-threshold dose (Dq), leading to an average tetrac enhancement factor (ratio of SF2 values) of 2.5. Tetrac reduced SLDR in exponential cells by a factor of 1.8. In plateau phase cells there was little expression of SLDR, but tetrac produced additional cell killing at 1-4 h after the first dose. For PLDR expression in exponential cells, tetrac inhibited PLDR by a factor of 1.9, and in plateau phase cells, tetrac decreased PLDR expression by a factor of 3.4. These data show that the decreased Dq value seen after single doses of x-rays with tetrac treatment is also accompanied by a significant decrease in recovery from sublethal and potentially lethal damage.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • Cell Survival / radiation effects*
  • Glioma*
  • Mice
  • Radiation Tolerance / drug effects*
  • Thyroxine / analogs & derivatives*
  • Thyroxine / pharmacology
  • X-Rays

Substances

  • Antineoplastic Agents
  • tetraiodothyroacetic acid
  • Thyroxine