Growth hormone protects against radiotherapy-induced cell death.
BACKGROUND
In vivo treatment with growth hormone reduces radiation-associated mortality. The molecular mechanisms underlying this effect are unknown. It has been described that increased sensitivity to ionising radiation can be due to defects in machinery involved in detection and/or repair of DNA double-strand breaks.


OBJECTIVE
To study the mechanisms involved in growth hormone action on the increased survival in irradiated cells.


METHODS
CHO-4 cells stably expressing the growth hormone receptor were used. A cell viability assay was carried out to analyse the increase in survival induced by growth hormone in irradiated cells. To investigate whether the DNA repair mechanism could be implicated in this effect we performed DNA reactivation assays using pHIV-LUC and pCMV-betagal plasmids as control. Identical studies were also conducted using the radiomimetic drug, bleomycin.


RESULTS
Growth hormone protects CHO-4 cells from bleomycin- and radiation-induced cell death. In pHIV-LUC transfected cells, a time-dependent decrease in luciferase activity was observed after irradiation in the absence of growth hormone. However, cells pretreated with this hormone maintained reporter activity. When cells were transfected with irradiated pHIV-LUC plasmid, only the hormone-treated cells recovered the transcriptional activity.


CONCLUSIONS
Growth hormone exerts a radioprotective effect in CHO-4 cells stably transfected with the complementary DNA for the rat growth hormone receptor. The radioprotection is triggered directly by the hormone and it is also observed with bleomycin. The increased survival in response to radiation and bleomycin treatment induced by growth hormone correlates with an enhanced ability of the cells to repair damaged DNA.
Madrid
Olga
O
Instituto de Investigaciones Biomedicas del CSIC/UAM, Arturo Duperier 4, Madrid 28029, Spain.
Varea
Silvia
S
Sanchez-Perez
Isabel
I
Gomez-Garcia
Lourdes
L
De Miguel
Enrique
E
Gomez De Segura
Ignacio A
IA
Perona
Rosario
R
D000818:Animals; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects* / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000166:cytology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014162:Transfection
D011837:Radiation-Protective Agents; D013006:Growth Hormone