Early Effects of Low Dose-Rate Radiation on Cultured Tumor Cells

Abstract

Low-dose hyperradiosensitivity (HRS) has been found for several cell types after exposure to low doses, < 0.5 Gy, of high dose-rate (typically 50-150 Gy/h) low-LET radiation. HRS precedes the occurrence of a relative resistance for doses above 0.5-1 Gy. A critical question is whether HRS is of importance in radionuclide therapy where the dose-rate is low but the total dose might be high. An indication that cells exposed to low dose-rate can be kept hyperradiosensitive has recently been published. We have in the present study applied cells without (glioma U373MG) and with (glioma U118MG and colon carcinoma HT29) HRS and studied early effects, up to one week, during low dose-rate (LDR), 0.05-0.09 Gy/hours, exposure (total dose after one week: 11.8 +/- 1.5 Gy). The cells were grown on thin foils above a (32)P source placed in a cell culture chamber. Cell number reductions, cell-cycle disturbances, and changed numbers of apoptotic cells were analyzed after continuous LDR exposures. There seemed to be no relation with HRS when the cell number reduction was considered. The U373MG cells, lacking HRS, had the strongest cell number reduction due to a combination of a G(2) block and increased apoptosis. The U118MG and HT29 cells, both having HRS, had surprisingly low cell number reductions. U118MG had only a G(2) block but no increase in apoptosis. HT29 had both a G(2) block and an increase in apoptosis but the apoptosis change was somewhat smaller than for U373MG. Thus, there seemed to be no obvious relation between HRS and early cellular effects when the cells were analyzed after continuous LDR exposure.

Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin

“…However, this remains controversial 18,23 and, moreover, this was reported in only one histological type of gastric cancer or cancer of other organs [24][25][26][27] Undifferentiated cancer cells are generally more sensitive to radiation. Thus, radiation effects may vary with cancer histology.…”

Relative Biological Effectiveness and Cell-Killing Efficacy of Continuous Low-Dose-Rate 125I Seeds on Prostate Carcinoma Cells In Vitro

“…A key molecular mechanism of radiation-induced cell death is via the activation of the apoptotic pathway. [27][28][29][30] Apoptosis represents an efficient and ubiquitous cellularsuicide pathway that involves the activation and inhibition of complex genetic events in response to cytotoxic stimuli. Triggering of the apoptotic process is regulated by several intracellular factors, such as the members of the Bcl-2 gene family, bax, cytochrome C, and caspases.…”

The biological effect of 125I seed continuous low dose rate irradiation in CL187 cells

“…Therefore, the apoptotic cells under 10 Gy were fewer than those under 5 Gy. Similarly, G 2 /M arrest also declined under 10 Gy [ 33 ].…”