Studies on the Relationship between the Radiation Resistance and Glutathione Content of Human and Rodent Cells after Treatment with Dexamethasonein Vitro

Abstract

A 20 h pre-treatment of human cells from normal (foetal lung) or malignant origin (glioma, lines U118 MG and U251 MG and bladder carcinoma, line EJ) with dexamethasone failed to increase their radiation resistance in vitro despite a 2-fold increase in the GSH content of a glioma cell line, U251 MG, and a small but significant increase in the GSH content of EJ bladder carcinoma cells. In contrast, there was a correlation between an increase in radiation resistance and an elevated GSH content of rodent cells (Chinese hamster lung, line V-79-379A; ovary, line CHO; rat hepatoma, line HTC, and mouse neuroblastoma, line NB413A) after a similar pre-treatment. The results suggest that enhancement of radiation resistance cannot be directly ascribed to an elevated GSH content in steroid-treated cells. On the basis of these data it is unlikely that the efficacy of radiotherapy will be diminished amongst patients receiving concomitant treatment with dexamethasone. However, in vivo testing is required to confirm these findings.

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

“…48 Similarly, GCs stimulated p21 gene expression by targeting multiple transcriptional elements within a steroid responsive region of the p21 WAF1/CIP1 promoter in rat hepatoma cells. 49 Another possibility, not examined in this study, is that DEX may have upregulated some drug-detoxifying factors such as found for metallothionein, [50][51][52] O6-methylguanine-DNA methyltransferase (MGMT), 53-55 P-glycoprotein 56,57 or glutathione, 58 which may have influenced the effectiveness of chemotherapy. 59…”

Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

“…However, dexamethasone-induced radioresistance does not occur in all human cell types. Dexamethasone did not confer radioresistance in breast carcinoma cell line MCF-7 nor in normal diploid fibroblast strain AG 1522 [2], nor in glioblastoma cell lines Ul18 MG and U251 MG [15].…”

Failure of betamethasone to alter the radiation response of two cultured human glioma cell-lines

“…Nederman et al [9] reported that there was a slight tendency towards radio-protection of human glioma cells during continuous exposure to betamethasone. Millar et al [10] reported that no changes in radiosensitivity could be seen when the same type of human glioma cells were treated with 1/~g/ml of dexamethasone. To sort out this discrepancy we decided to carry out a more extensive study using a continuous exposure of betamethasone.…”

“…To sort out this discrepancy we decided to carry out a more extensive study using a continuous exposure of betamethasone. The study by Nederman et al [9] on the effects of betamethasone was very limited while the study by Millar et al [10] on dexamethasone was carried out in more detail. Cultured glioma cells are known to have a low cloning efficiency [10,11] and it is therefore difficult to clone them according to the original description by Puck and Marcus [12].…”

“…The study by Nederman et al [9] on the effects of betamethasone was very limited while the study by Millar et al [10] on dexamethasone was carried out in more detail. Cultured glioma cells are known to have a low cloning efficiency [10,11] and it is therefore difficult to clone them according to the original description by Puck and Marcus [12]. An alternative method to obtain radiation survival parameters is to use the extrapolation method, which has been previously described to be a reliable and easily handled method [13,14].…”