Growth hormone protects against radiotherapy-induced cell death

Abstract

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. Materials and 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-bgal 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.

The oncogenic potential of growth hormone

“…Treatment of irradiated or aged mice with rhGH significantly reduced bone marrow hypocellularity and restored haematopoiesis [60] while a fourth study has demonstrated decreased severity of radiotherapy-induced dermatitis in rats consequent of GH administration [61]. GH administration also protects Chinese hamster ovary cells stably expressing the GHR from radiation and bleomycin-induced cell death [62]. The beneficial aspects of hGH administration in these settings is apparent; however with recent evidence implicating hGH in oncogenesis, perhaps caution should taken when translating these findings into a clinical setting.…”

Autocrine human GH promotes radioresistance in mammary and endometrial carcinoma cells

“…Due to evidence suggesting a radioprotective role for GH (Gomez-de-Segura et al 1998, Vazquez et al 1999, Mylonas et al 2000, Isla et al 2002, Madrid et al 2002, Raguso et al 2002, Lempereur et al 2003, N M Bougen et al: Autocrine human GH is radioprotective www.endocrinology-journals.org Morante et al 2003, Tekin et al 2006, we investigated whether autocrine hGH enhanced mammary and endometrial cancer cell viability following treatment with IR. Three pairs of stably transfected cell lines (MDA-vec and MDA-hGH, T47D-vec and T47D-hGH and RL95-vec and RL95-hGH cells) were exposed to an initial treatment range of 0-8 Gy IR.…”

“…Although we did not observe any effect on the DNA repair capacity using the neutral comet assay, an effect on DNA repair cannot be ruled out. A study by Madrid et al (2002) demonstrated that the radioprotective effect mediated by exogenous GH in CHO-4 cells stably expressing the GHR was associated with an enhanced ability of the cells to repair damaged DNA, indicating that GH may activate pathways involved in DNA repair processes. Further investigation using assays interrogating different DNA repair pathways would determine whether autocrine hGH impacted on the DNA repair capacity of breast and endometrial cancer cell lines.…”

“…Treatment of Chinese hamster ovarian (CHO-4) cells stably expressing the GHR with exogenous hGH protects them from cell death induced by g-irradiation or the radiomimetic drug bleomycin in a dose-dependent manner (Madrid et al 2002). Treatment of irradiated rat pituitary cells or human peripheral blood lymphocytes with recombinant GH increases cell survival (Chiarenza et al 2000, Lempereur et al 2003.…”

Hormones and breast cancer: can we use them in ways that could reduce the risk?

“…IGFBP-3 inhibits estrogen induced proliferation of breast cancer cells as well as promoting apoptosis of cancer cells [76]. HGH repairs DNA damage inflicted on cells by carcinogens and radiation [77]. It increases the activity of "Natural Killer Cells" [78].…”