Radiosensitization of GL261 glioma cells by tetraiodothyroacetic acid (tetrac).
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.
Hercbergs
Aleck
A
The Cleveland Clinic, Department of Radiation Oncology, Cleveland, OH 44195, USA. hercbergs@gmail.com
Davis
Paul J
PJ
Davis
Faith B
FB
Ciesielski
Michael J
MJ
Leith
John T
JT
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D005910:Glioma; D051379:Mice; D011836:Radiation Tolerance / Q000187:drug effects*; D013974:Thyroxine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014965:X-Rays
D000970:Antineoplastic Agents; C011126:tetraiodothyroacetic acid; D013974:Thyroxine