The radiation dose-rate effect in two human neuroblastoma cell lines

Abstract

Summary The current use of targeted radiotherapy in the treatment of neuroblastoma has generated a requirement for further information on the radiobiology of these cells. Here we report on studies of the dose-rate effect in two human neuroblastoma cell lines (HX138 and HX142) and the recovery that they demonstrate in split-dose experiments. The sensitivity of the two cell lines to high dose-rate irradiation was confirmed. Surviving fractions at 2 Gy were 0.083 for HX138 anc' 0.11 for HX142. There was little evidence of a dose-rate effect above 2 cGy min-' but significant sparing was seen at lower dose rates. Substantial recovery was seen in split-dose experiments on both cell lines, to an extent that was consistent with the linear quadratic equation. The data were used to derive values for the P parameter of the linear-quadratic equation; the values for the neuroblastomas were higher than for any of the other human tumour cell lines that we have investigated to date. Thus, despite their high sensitivity to ionising radiation HX138 and HX142 do exhibit substantial levels of cellular recovery, suggesting that they may have a significant capacity for repair of radiation-induced lesions.Human neuroblastoma is a childhood tumour which is generally regarded as being radioresponsive even though external-beam radiotherapy plays a minor role in its management (Jacobson et al., 1983). As a result of the relatively specific uptake into these tumours of MIBG, the treatment of patients with systemically-administered '1I-MIBG is increasingly being performed (Pinkerton, 1990). There is therefore a need for more detailed understanding of the response to ionising radiation in neuroblastoma.Recent work in this department has drawn attention to the fact that radiosensitive human tumour cells may not be recovery-deficient (Peacock et al., 1988) and that radiation split-dose recovery increases continuously with dose. We have therefore set out in this study to compare the results of low dose-rate and multiple-dose-level split-dose experiments in two neuroblastoma cell lines. This is the final report of a project from which parts of the data have appeared in an interim form (Peacock et al., 1988. tubes (Falcon). After allowing the agar to set on ice, the cultures were gassed in a 3%, 02, 5% CO2, 92% N2 atmosphere for a minimum of 2 hours and sealed.All Comparison of the data with mathematical models was carried out using methods described previously (Steel et al., 1987). Results Materials and methods Cell linesThe two cell lines used here, HX138 and HX142 were established from xenografted tumour tissue by Dr J.M. Deacon in this department The data on HX142 are at five reduced dose rates ( Figure 3). Again, there is little dose-rate effect for rates in excess of I cGy min-'.Each set of data has been fitted with the linear quadratic equation and the resulting parameters are shown in Table I. Comparison between the cell lines is facilitated by plotting isoeffect curves; Figure 4 shows the dose (DO.01) required to produce a surviving fr...

Effects of Dose Rate on the Reproductive Cell Death and Early Mitochondrial Membrane Potential in Different Human Epithelium-Derived Cells Exposed to Gamma Rays

“…Similar observations were previously made with human neuroblastoma cells receiving g rays at a dose rate range of 10 to 900 mGy/min; however, a lower dose rate of 2.5 mGy/min was found to have a less deleterious effect. 22 For human normal dermal fibroblasts and melanoma cells following X-ray irradiation, 1120 mGy/min was much more damaging than 8.8 mGy/min. 23 Enn et al (2004) found that there was no major dose rate effect (1.8 vs 220 mGy/min) in human lung adenocarcinoma cells A549.…”

“…The lowest dose rate of 24.6 mGy/min was in a range that would be considered low in radiation oncology and cellular radiobiology experiments. [21][22][23][24] However, 24.6 mGy/min is relatively higher than both the environmental contamination/occupational exposure levels associated with radioactive fallout accidents [25][26][27][28] and the UNSCEAR's recommended low dose rate of <0.1 mGy/min (UNSCEAR 2012). 29 The other 3 dose rates used here would generally be considered high.…”

A Model of Photon Cell Killing Based on the Spatio-Temporal Clustering of DNA Damage in Higher Order Chromatin Structures

“…The experimental values were gained with exponential recovery fits to split dose experiments [21] , [33] , [36] , [37] . The listed values resulting from a fit of the Incomplete Repair model (IR model) or the Lethal Potentially Lethal model (LPL model) to cell survival curves are taken from the following publications: [36] , [37] , [40] . The values given for the GLOBLE (which correspond to HLT i ) were determined with fits to experimentally measured cell survival data as shown in the results of this paper.…”

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with131I-mIBG

“…For instance, Courdi et al (1992) reported a value of 1.85 Gy for the CHP100 cell line, Holmes et al (1990) gave values of 5.00 Gy for the HX138 cell line and 9.38 Gy for the HX142 cell line, and Marchese et al (1987) reported a value of 17.59 Gy for the SK-N-SH cell line. In Fertil and Malaise (1985), Malaise et al (1987) and Amin et al (1995), NB was included among highly responsive tumours and values of 7.11 Gy, 8.31 Gy and 13.08 Gy were respectively reported.…”