Increased radiation toxicity by enhanced apoptotic clearance of HL-60 cells in the presence of the pentapeptide thymopentin, which selectively binds to apoptotic cells.
Radiotoxic insult to cells is associated with genetic instability and heritable damage [Mutat. Res. 517 (2002) 173]. A strengthened response to such insult by enhanced apoptotic clearance, which would be associated with anti-inflammatory [Nature 390 (1997) 350; Nature 407 (2000) 784] and anti-necrotic intercellular signaling [Nature 418 (2002) 191], has been previously reported. The pentapeptide thymopentin (TP5) improves immunological parameters in cancer patients following radiotherapy without clinically observable side effects. We assessed the effects of TP5 on human promyeloid leukemia HL-60 cells exposed to therapeutic (2Gy) doses of X-rays. We observed an increased accumulation of cells in the G2/M phase of the cell cycle after irradiation when treated with TP5. However, TP5 had no effect on the cell cycle distribution of non-irradiated HL-60 cells. Additionally, TP5 treatment of irradiated cells increased the number of cells undergoing apoptosis. Furthermore, TP5 was found to selectively bind to apoptotic cells. These findings represent a promising and novel approach employing TP5-mediated modulation of cellular radiation response to augment both clinical gain in radiation oncology and safety measures for radiation protection.
Gonser
Susanne
S
Department of Pharmacy, ETH Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Crompton
Nigel E A
NE
Folkers
Gerd
G
Weber
Erich
E
D002453:Cell Cycle; D018922:HL-60 Cells; D006801:Humans; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D016305:Thymopentin / Q000378:metabolism / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D016305:Thymopentin