HIGH AND LOW-DOSE RATE IRRADIATION HAVE OPPOSING EFFECTS ON CYTOKINE GENE-EXPRESSION IN HUMAN GLIOBLASTOMA CELL-LINES

Effects of radiation on five cytokine expressing human glioblastoma ce ll lines were studied. In comparison to unirradiated controls, IL-1 be ta and IL-6 mRNAs were generally reduced after low (LDR, 1.0 cGy/min) and very low (VLDR, 0.35 cGy/min) dose rate irradiation. In contrast, high (HDR, 200 cGy/min) and intermediate (IDR, 4.1 cGy/min) dose rates increased steady-state levels of IL-1 beta and IL-6 mRNAs. The surviv ing fraction was generally inversely proportional to the dose rate; ho wever, these glioma cells were unusually susceptible to LDR. In the tw o cell lines tested, IDR was less cytotoxic than either HDR or LDR irr adiation. Although cytokine gene expression had no clear effect on rad iation survival in vitro, autologous cytokines could be important to r adiation response in vivo by affecting immune response, tumour stroma, vasculature or surrounding tissues. Adjusting dose rates to account f or inverse dose rate effects and altered gene expression may be a usef ul strategy in optimising radiation therapy of glioblastomas. (C) 1997 Elsevier Science Ltd.