The Effect of Hypoxia on Relative Biological Effectiveness and Oxygen Enhancement Ratio for Cells Irradiated with Grenz Rays

Abstract

Grenz-ray therapy (GT) is commonly used for dermatological radiotherapy and has a higher linear energy transfer, relative biological effectiveness (RBE) and oxygen enhancement ratio (OER). GT is a treatment option for lentigo maligna and lentigo maligna melanoma. This study aims to calculate the RBE for DNA double-strand break (DSB) induction and cell survival under hypoxic conditions for GT. The yield of DSBs induced by GT is calculated at the aerobic and hypoxic conditions, using a Monte Carlo damage simulation (MCDS) software. The RBE value for cell survival is calculated using the repair-misrepair-fixation (RMF) model. The RBE values for cell survival for cells irradiated by 15 kV, 10 kV and 10 kVp and titanium K-shell X-rays (4.55 kV) relative to ⁶⁰Co γ-rays are 1.0-1.6 at the aerobic conditions and moderate hypoxia (2% O₂), respectively, but increase to 1.2, 1.4 and 1.9 and 2.1 in conditions of severe hypoxia (0.1% O₂). The OER values for DSB induction relative to ⁶⁰Co γ-rays are about constant and ~2.4 for GT, but the OER for cell survival is 2.8-2.0 as photon energy decreases from 15 kV to 4.55 kV. The results indicate that GT results in more DSB induction and allows effective tumor control for superficial and hypoxic tumors.

Keywords: Grenz rays; cell survival; double strand break; hypoxia; oxygen enhancement ratio; relative biological effectiveness.

Figure 1

Percentage of double-strand break (DSB) induction as a function of oxygen concentration: the symbol Ti denotes titanium K-shell.

Figure 2

(A) Oxygen enhancement ratio (OER) for double-strand break (DSB) induction for cells irradiated by photons. The lines are the Monte Carlo damage simulation (MCDS) results and those for other Monte Carlo simulations [69]. The individual symbols represent the experimental OER values for V79 cells [17,61], Chinese hamster ovary (CHO) cells [38] and human non-small cell lung cancer A549 cells [70]. (B) OER for cell survival at 10% as a function of linear energy transfer (LET) and mean photon energy. These measured OER values are from published studies: CHO cells [38,39,71], Hela cells [72] and V79 cells irradiated with photons [17,18,40,73,74] and protons [18].

Figure 2

(A) Oxygen enhancement ratio (OER) for double-strand break (DSB) induction for cells irradiated by photons. The lines are the Monte Carlo damage simulation (MCDS) results and those for other Monte Carlo simulations [69]. The individual symbols represent the experimental OER values for V79 cells [17,61], Chinese hamster ovary (CHO) cells [38] and human non-small cell lung cancer A549 cells [70]. (B) OER for cell survival at 10% as a function of linear energy transfer (LET) and mean photon energy. These measured OER values are from published studies: CHO cells [38,39,71], Hela cells [72] and V79 cells irradiated with photons [17,18,40,73,74] and protons [18].

Figure 3

Relative biological effectiveness (RBE) values for cells irradiated by ultrasoft X-rays as a function of linear energy transfer (LET). (A) The repair–misrepair–fixation (RMF)-model-predicted RBE values for cell survival at 10% are plotted for oxygen concentrations of 21% (solid line), 2% (dash-dotted line) and 0.1% (dotted line). The experimental RBE values were measured at an oxygen concentration of 21% O₂ for V79 cells [17,75,76], Chinese hamster ovary (CHO) cells [75] and human mammary epithelial cell line MCF-12A [77] after photon irradiations. (B)The values for parameter α using RMF model: the equations for the α value under aerobic and hypoxic conditions are, respectively, α = 0.0466 × LET + 0.2412 (R² = 0.9443) (21% O₂) and α = 0.0402 × LET + 0.0466 (R² = 0.9161) (0.1% O₂). These measured α values are from published studies: CHO cells and V79 cells irradiated with photons at an aerobic condition (21% O₂) [61,71,75] and at a hypoxic condition (0.1% O₂) [61,71].

Figure 3

Relative biological effectiveness (RBE) values for cells irradiated by ultrasoft X-rays as a function of linear energy transfer (LET). (A) The repair–misrepair–fixation (RMF)-model-predicted RBE values for cell survival at 10% are plotted for oxygen concentrations of 21% (solid line), 2% (dash-dotted line) and 0.1% (dotted line). The experimental RBE values were measured at an oxygen concentration of 21% O₂ for V79 cells [17,75,76], Chinese hamster ovary (CHO) cells [75] and human mammary epithelial cell line MCF-12A [77] after photon irradiations. (B)The values for parameter α using RMF model: the equations for the α value under aerobic and hypoxic conditions are, respectively, α = 0.0466 × LET + 0.2412 (R² = 0.9443) (21% O₂) and α = 0.0402 × LET + 0.0466 (R² = 0.9161) (0.1% O₂). These measured α values are from published studies: CHO cells and V79 cells irradiated with photons at an aerobic condition (21% O₂) [61,71,75] and at a hypoxic condition (0.1% O₂) [61,71].