Effect of somatostatin on repair of ionizing radiation-induced DNA damage in pituitary adenoma cells GH3.
Ionizing radiation and somatostatin analogues are used for acromegaly treatment to achieve normalization or reduction of growth hormone hypersecretion and tumor shrinkage. In this study, we investigated a combination of somatostatin (SS14) with ionizing radiation of (60)Co and its effect on reparation of radiation-induced damage and cell death of somatomammotroph pituitary cells GH3. Doses of gamma-radiation 20-50 Gy were shown to inhibit proliferation and induce apoptosis in GH3 cells regardless of somatostatin presence. It has been found that the D(0) value for GH3 cells was 2.5 Gy. Somatostatin treatment increased radiosensitivity of GH3 cells, so that D(0) value decreased to 2.2 Gy. We detected quick phosphorylation of histone H2A.X upon irradiation by the dose 20 Gy and its colocalization with phosphorylated protein Nbs-1 in the site of double strand break of DNA (DSB). Number of DSB decreased significantly 24 h after irradiation, however, clearly distinguished foci persisted, indicating non repaired DSB, after irradiation alone or after combined treatment by irradiation and SS14. We found that SS14 alone triggers phosphorylation of Nbs1 (p-Nbs1), which correlates with antiproliferative effect of SS14. Irradiation also increased the presence of p-Nbs1. Most intensive phosphorylation of Nbs1 was detected after combined treatment of irradiation and SS14. The decrease of the number of the DSB foci 24 h after treatment shows a significant capacity of repair systems of GH3 cells. In spite of this, large number of unrepaired DSB persists for 24 h after the treatment. We conclude that SS14 does not have a radioprotective effect on somatomammotroph GH3 cells.
Řezáčová
M
M
Dept. of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Hradec Králové, Czech Republic. rezacovam@lfhk.cuni.cz
Čáp
J
J
Vokurková
D
D
Lukášová
E
E
Vávrová
J
J
Cerman
J
J
Mašín
V
V
Mazánková
N
N
D000172:Acromegaly / Q000188:drug therapy / Q000601:surgery*; D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000528:radiation effects; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy* / Q000601:surgery; D006657:Histones / Q000378:metabolism / Q000528:radiation effects; D009687:Nuclear Proteins / Q000378:metabolism / Q000528:radiation effects; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000601:surgery; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000517:prevention & control; D011839:Radiation, Ionizing; D016634:Radiosurgery / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000502:physiology* / Q000627:therapeutic use; D052683:Somatotrophs / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D018709:Statistics, Nonparametric
D018797:Cell Cycle Proteins; D006657:Histones; D009687:Nuclear Proteins; D013004:Somatostatin