Relative biological effectiveness (RBE) of alpha radiation in cultured porcine aortic endothelial cells

PURPOSE: Northern peoples can receive elevated radiation doses (1- 10 mSv/y) from transfer of polonium-210 (210Po) through the lichen-caribou-human food chain. Ingested 210Po is primarily blood-borne and thus many of its short range alpha particles irradiate the endothelial cells lining the blood vessels. The relative biological effectiveness (RBE) of alpha particles vs. x-rays was examined in porcine aortic endothelial cells as a surrogate for understanding what might happen to human endothelial cells in northern populations consuming traditional foods. MATERIALS AND METHODS: Cultured porcine aortic endothelial cells were exposed to x-ray and 210Po alpha particle radiation. Alpha irradiation was applied to the cell cultures internally via the culture medium and externally, using thin-bottomed culture dishes. The results given here are based on the external irradiation method, which was found to be more reliable. Dose-response curves were compared for four lethal endpoints (cell viability, live cell fraction, release of lactate dehydrogenase [LDH] and clonogenic survival) to determine the relative biological effectiveness (RBE) of alpha radiation. RESULTS: The alpha RBE for porcine cells varied from 1.6-21, depending on the endpoint: 21.2+/-4.5 for cell viability, 12.9+/-2.7 for decrease in live cell number, 5.3+/-0.4 for LDH release to the medium but only 1.6 +/-0.1 for clonogenic survival. The low RBE of 1.6 was due to x-ray hypersensitivity of endothelial cells at low doses.     

重离子生物效应的研究进展

重离子是一种具有特殊物理性质的带电离子,在射程末端可形成Bragg峰。与X射线、γ射线等低传能线密度（LET）射线相比具有较高的相对生物效应。笔者从细胞水平和分子水平简要介绍了重离子的辐射生物效应,以及与低LET射线的主要区别。     

Relative biological effectiveness (RBE) of 210Po alpha-particles versus X-rays on lethality in bovine endothelial cells

PURPOSE: Alpha-radiation from polonium-210 ((210)Po) can elevate background radiation dose by an order of magnitude in people consuming large quantities of meat and seafood, particularly caribou and reindeer. Because up to 50% of the ingested (210)Po body burden is initially found in the blood, a primary target for the short range alpha-particles is the endothelial cells lining the blood vessels. This study examined the relative biological effectiveness (RBE) of (210)Po alpha-particles versus 250 kVp X-rays in producing injury to cultured bovine aortic endothelial cells. MATERIALS AND METHODS: Radiation effects on cells were measured in four different ways: the percentage viable cells by trypan blue dye exclusion, the number of live cells, the lactate dehydrogenase (LDH) release to medium and the ability to form colonies (clonogenic survival). RESULTS: Comparison of dose-response curves yielded RBE values of 13.1+/-2.5 (SEM) for cell viability, 10.3+/-1.0 for live cell number and 11.1+/-3.0 for LDH activity. The RBE values for clonogenic survival were 14.0+/-1.0 based on the ratio of the initial slopes of the dose-response curves and 13.1, 9.9 and 7.7 for 50, 10 and 1% survival rate, respectively. At X-ray doses <0.25 Gy, a pronounced stimulatory effect on proliferation was noted. CONCLUSIONS: Exposure to (210)Po alpha-particles was seven to 14 times more effective than X-ray exposure in causing endothelial cell damage.     

Relative biological effectiveness of accelerated heavy ions and fast neutrons estimated from frequency of aberration mytoses in the retinal epithelium]

Analyzed was the literature and authors' experimental data concerning lesion and recovery of epithelium cells of mice retina immediately and long after irradiation at different sources including single and partly fractionated irradiation by gamma- and X-rays, accelerated protons, helium, carbon and boron ions, and fast neutrons of the reactor range in a large spectrum of doses and LET. Reviewed are some new techniques of determining the RBE coefficient for these types of radiation; large values of the RBE coefficients for accelerated ions and neutrons (5-10 times higher than RBE coefficients calculated for the next day following irradiation) are a result of integration into calculation of the available data about the delayed disorders in retinal epithelium cell regeneration.     

Relative biological effectiveness (RBE) of 210 Po alpha-particles versus X-rays on lethality in bovine endothelial cells

Purpose : Alpha-radiation from polonium-210 (210 Po) can elevate background radiation dose by an order of magnitude in people consuming large quantities of meat and seafood, particularly caribou and reindeer. Because up to 50% of the ingested 210 Po body burden is initially found in the blood, a primary target for the short range alpha-particles is the endothelial cells lining the blood vessels. This study examined the relative biological effectiveness (RBE) of 210 Po alpha-particles versus 250 kVp X-rays in producing injury to cultured bovine aortic endothelial cells. Materials and methods : Radiation effects on cells were measured in four different ways: the percentage viable cells by trypan blue dye exclusion, the number of live cells, the lactate dehydrogenase (LDH) release to medium and the ability to form colonies (clonogenic survival). Results : Comparison of dose-response curves yielded RBE values of 13.1 ±2.5 (SEM) for cell viability, 10.3 ±1.0 for live cell number and 11.1 ±3.0 for LDH activity. The RBE values for clonogenic survival were 14.0 ±1.0 based on the ratio of the initial slopes of the dose-response curves and 13.1, 9.9 and 7.7 for 50, 10 and 1% survival rate, respectively. At X-ray doses <0.25 Gy, a pronounced stimulatory effect on proliferation was noted. Conclusions : Exposure to 210 Po alpha-particles was seven to 14 times more effective than X-ray exposure in causing endothelial cell damage.     

Relative biological effectiveness of boron ions on human melanoma cells

Purpose : To compare the difference in relative biological effectiveness (RBE) between 10 B ions and a 60 Co γ-ray beam for human melanoma cells using in vitro cell survival based on a clonogenic assay. Materials and methods : Cells were irradiated in vitro under aerobic conditions with 60 Co and 10 B ions with different linear energy transfer (LET) (40, 80 and 160 eV nm -1) . The dose to the cells was determined using ferrous sulphate dosimetry and an ionisation chamber. The standard linear-quadratic model and the newly proposed repairable conditionally repairable damage (RCR) model were used to calculate the RBE. Results : The RBE at 10% cell survival for 40, 80 and 160eV nm -1 boron ions compared with 60 Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17-3.58), respectively, of almost independence of the model used in the calculation. Conclusions : Different cell survival models may generate different RBE, especially at low doses and high cell survival levels.     

Relative biological effectiveness of boron ions on human melanoma cells

PURPOSE: To compare the difference in relative biological effectiveness (RBE) between (10)B ions and a (60)Co gamma-ray beam for human melanoma cells using in vitro cell survival based on a clonogenic assay. MATERIALS AND METHODS: Cells were irradiated in vitro under aerobic conditions with (60)Co and (10)B ions with different linear energy transfer (LET) (40, 80 and 160 eV nm(-1)). The dose to the cells was determined using ferrous sulphate dosimetry and an ionisation chamber. The standard linear-quadratic model and the newly proposed repairable conditionally repairable damage (RCR) model were used to calculate the RBE. RESULTS: The RBE at 10% cell survival for 40, 80 and 160 eV nm(-1) boron ions compared with (60)Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17-3.58), respectively, of almost independence of the model used in the calculation. CONCLUSIONS: Different cell survival models may generate different RBE, especially at low doses and high cell survival levels.     

A comparison of methods to calculate biological effectiveness (RBE) from Monte Carlo simulations.

The relative biological effectiveness (RBE) of radiation is assessed and easily calculated by Monte Carlo simulations of the passage of radiation through matter. The expression to calculate the RBE provided by microdosimetry requires the use of the energy spectrum of charged particles. This paper compares the RBE values obtained for Palladium-103 (103Pd) and iodine-125 (125I) when calculated with 2 different spectra: the electron slowing-down spectrum and the ejection spectrum. The former yields a value of 10.6%, twice the value obtained with the latter (4.5%). Which spectrum to use is an open question. A theoretical argument is presented in favor of the ejection spectrum.     

Treatment planning for light ions: How to take into account Relative Biological Effectivness (RBE)

A new treatment planning program was developed for the heavy ion therapy facility at GSI, which is tailored to the special needs for an active beam delivery using a magnetic raster scanner. It also includes a biological model for the estimation of biological effective dose for carbon ions and realizes a fully biological treatment planning. Biological effective dose distributions and RBE maps can be displayed and assessed from the graphical user interface.

     

Relative biological effectiveness (RBE) of p(26) + Be neutrons from the King Faisal Specialist Hospital and Research Centre CS-30 cyclotron measured by testis weight loss

Testis weight loss of C3H and Swiss-Webster (SW) mice was used as endpoint to determine the relative biological effectiveness (RBE) of p(26) + Be fast neutrons with respect to Co-60 gamma irradiation. Percent weight loss versus dose curves showed two components. Comparing first component effects, the RBE was 3.4 (C3H) and 3.7 (SW); when the second component was used, the RBE was 2.6 and 2.7 (C3H), and 3.5 (SW). When percent weight loss was plotted versus log dose, parallel lines were obtained, giving an RBE of 3.9 and 4.1 (C3H), and 4.2 (SW). Results were compared with published values and RBE as a function of fast neutron energy was plotted. A good correlation was found. Discrepancies seem to be mostly due to the use of different baseline radiation. When a constant correction is made, most of the values fit a single line. The possibility of using this approach as a substitute for international comparisons is discussed.     

Calculation of the relative biological efficiency (RBE) of neutron radiation

The Relative Biological Effectiveness (RBE) of radiation with different LET has to be recognized in the planning of radiation therapy especially if one type of radiation should be replaced by another type or if both should be used within the same irradiation course. In radiation therapy it is suitable to consider the RBE in connection with dose dependent cell survival rates. These rates can be described by means of corresponding mathematical models. A simple way to calculate the RBE on the basis of the modern LQ-model is demonstrated. In that procedure the alpha/beta-ratios which are known at least approximatively for many organs and tissues can be used. The proposed method is demonstrated for the human skin and lung. For these organs we obtained RBE ranges from 3.4 to 1.2 and from 3.8 to 0.8, respectively, considering increasing doses. Thereby, for the lung it can be observed that the dose dependency of the RBE for small doses is especially strong. The obtained results are in good coincidence with experiences in clinical practice.     

The general relation between tissue response to x-radiation (alpha/beta-values) and the relative biological effectiveness (RBE) of protons: prediction by the Katz track-structure model

PURPOSE: Experimental data suggest that the relative biological effectiveness (RBE) of protons compared to x-rays may be determined by the alpha/beta-ratio of the x-ray survival curve. The data are referring to the centre of a spread-out Bragg peak (SOBP) formed to deliver a homogeneous dose to the tumour by modulating the proton energy. In an effort to explore the basis for this observation, calculations were performed to investigate the response of different biological targets through a range of proton energies and doses. MATERIALS AND METHODS: To describe the x-ray survival curve, the parameters of the linear-quadratic equation, alpha and beta, as well as those of the multi-target/single-hit equation, n and D0, were considered. These parameters were varied to investigate the RBE using the Katz track-structure model. Known cell line characterizations, as well as different hypothetical cells assuming different alpha/beta-ratios but similar target size parameters in the framework of the track-structure theory, were considered. RESULTS: The RBE was found to increase with increasing alpha/beta when the parameter n was varied, but to decrease with increasing alpha/beta when D0 was varied. This held when all other radiosensitivity parameters were assumed to stay constant. Thus, the RBE cannot be predicted by the alpha/beta-ratio alone. CONCLUSIONS: Although there is no direct correlation between the proton RBE and the parameters describing the x-ray survival curve, the track-structure model predicts a tendency for late-responding tissues (low alpha/beta) to have higher RBE values than early-responding tissues (high alpha/beta). These calculations reinforce the experimental findings, but also strongly suggest that there are circumstances in which the tendency for RBE to increase with increasing alpha/beta does not occur, or even could be reversed.