Growth hormone protects against radiotherapy-induced cell death

Area of Science:

• Cell biology
• Molecular biology
• Radioprotection

Background:

• Growth hormone (GH) administration in vivo reduces mortality associated with radiation exposure.
• The precise molecular mechanisms behind GH's radioprotective effects remain largely unknown.
• Defects in DNA double-strand break detection and repair machinery can increase sensitivity to ionizing radiation.

Purpose of the Study:

• To elucidate the mechanisms by which growth hormone enhances survival in irradiated cells.
• To investigate the role of DNA repair pathways in GH-mediated radioprotection.

Main Methods:

• Utilized CHO-4 cells engineered to stably express the growth hormone receptor.
• Assessed cell viability following irradiation and treatment with GH.
• Employed DNA reactivation assays with reporter plasmids (pHIV-LUC, pCMV-betagal) to evaluate DNA repair efficiency.
• Investigated effects using the radiomimetic drug bleomycin.

Main Results:

• Growth hormone significantly protected CHO-4 cells from both radiation- and bleomycin-induced cell death.
• Irradiated cells pretreated with GH maintained higher reporter gene activity compared to untreated cells.
• GH treatment facilitated the recovery of transcriptional activity in cells transfected with damaged DNA plasmids.

Conclusions:

• Growth hormone demonstrates a significant radioprotective effect in cells expressing its receptor.
• This radioprotection, also observed with bleomycin, is directly mediated by GH.
• GH-induced enhancement of cell survival correlates with an improved capacity for DNA damage repair.