NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

General correlations are found between the detailed spatial and temporal nature of the initial physical features of radiation insult and the likelihood of final biological consequences. These persist despite the chain of physical, chemical and biological processes that eliminate the vast majority of the early damage. Details of the initial conditions should provide guidance to critical features of the most relevant early biological damage and subsequent repair. Ionizing radiations produce many hundreds of different simple chemical products in DNA and also multitudes of possible clustered combinations. The simple products, including single-strand breaks, tend to correlate poorly with biological effectiveness. Even for initial double-strand breaks, as a broad class, there is apparently little or no increase in yield with increasing ionization density, in contrast with the large rise in relative biological effectiveness for cellular effects. Track structure analysis has revealed that clustered DNA damage of ...

Initial events in the cellular effects of ionizing radiations: clustered damage in DNA.

A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci.

(1983). Ionizing Radiation: Sources and Biological Effects. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine: Vol. 43, No. 5, pp. 585-586.

Ionizing Radiation: Sources and Biological Effects

Proton therapy treatments are based on a proton RBE (relative biological effectiveness) relative to high-energy photons of 1.1. The use of this generic, spatially invariant RBE within tumors and normal tissues disregards the evidence that proton RBE varies with linear energy transfer (LET), physiological and biological factors, and clinical endpoint.Based on the available experimental data from published literature, this review analyzes relationships of RBE with dose, biological endpoint and physical properties of proton beams. The review distinguishes between endpoints relevant for tumor control probability and those potentially relevant for normal tissue complication. Numerous endpoints and experiments on sub-cellular damage and repair effects are discussed.Despite the large amount of data, considerable uncertainties in proton RBE values remain. As an average RBE for cell survival in the center of a typical spread-out Bragg peak (SOBP), the data support a value of ~1.15 at 2 Gy/fraction. The proton RBE increases with increasing LETd and thus with depth in an SOBP from ~1.1 in the entrance region, to ~1.15 in the center, ~1.35 at the distal edge and ~1.7 in the distal fall-off (when averaged over all cell lines, which may not be clinically representative). For small modulation widths the values could be increased. Furthermore, there is a trend of an increase in RBE as (α/β)x decreases. In most cases the RBE also increases with decreasing dose, specifically for systems with low (α/β)x. Data on RBE for endpoints other than clonogenic cell survival are too diverse to allow general statements other than that the RBE is, on average, in line with a value of ~1.1.This review can serve as a source for defining input parameters for applying or refining biophysical models and to identify endpoints where additional radiobiological data are needed in order to reduce the uncertainties to clinically acceptable levels.

https://iopscience.iop.org/article/10.1088/0031-9155/59/22/R419/pdf

Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer

SummaryInactivation and mutation to thioguanine-resistance of V79 hamster cells were studied after irradiation with accelerated helium, boron or nitrogen ions covering a range of linear energy transfer from 28 to 470 keV µm−1. For all radiation qualities a dose-dependent increase in mutant frequency was found for doses giving surviving fractions greater than about 0·20. The effectiveness per unit dose for both inactivation and mutation induction increased with the linear energy transfer of the radiation to a maximum in the range 90–200 keV µm−1. However, the maximum mutagenic effectiveness relative to γ-rays was about two or more times that for inactivation. It is suggested that a proportion of the radiation-induced mutants suffer extensive genetic damage, and that some forms of this damage may be induced with high efficiency by radiations of high linear energy transfer.

Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions. II. Chinese hamster V79 cells.

A direct comparison was carried out of the biological effectiveness of protons and alpha-particles of the same linear energy transfer (LET) under identical conditions with a variety of in vitro biological systems. Monolayers of mammalian cells were irradiated with accelerated beams of protons (1.2 and 1.4 MeV) and alpha-particles (30 and 35 MeV) corresponding to LETs of 23 and 20 keV microns-1 for each particle type. For V79-4 cells it was observed that the linear term of the dose-response for cell inactivation by protons was significantly greater than that for alpha-particles of the same LET. For HeLa and HeLa S3 cells, also, the linear term appeared to be greater for protons, but this was not observed with more limited data for C3H 10T1/2 cells. The result for V79 cells is in agreement with the report of Belli et al. (1989) who observed that the biological effectiveness of protons rose sharply between 17 and 30 keV microns-1 in strong contrast to alpha-particles which reached a peak effectiveness at greater than 100 keV microns-1. These results place new constraints on the biologically relevant features of the microscopic structure of radiation tracks, and have implications for the mechanistic and practical comparison between radiations.

Direct comparison between protons and alpha-particles of the same LET: I. Irradiation methods and inactivation of asynchronous V79, HeLa and C3H 10T1/2 cells.

Summary The induction of mutation to purine analogue resistance was assessed in Chinese hamster V79-4 cells exposed to γ-radiation. After irradiation, the cells were grown in non-selective medium for different time intervals before respread-ing into medium containing 0.5–0.7 μ g/ml thioguanine. In some experiments colonies arising in thioguanine-medium were counter-selected in medium containing the glutamine analogue azaserine, which distinguishes mutants with very little activity of the enzyme hypoxanthine-guanine phosphoribosyl transferase. Only these mutants were increased in frequency by radiation, the maximum measured frequencies occurring in cells respread after 2 days growth in nonselective medium. With longer intervals of post-irradiation growth in non-selective medium a fraction of the induced mutants was lost, and after large doses of radiation it is doubtful if the maximum frequency observed after 2 days post-irradiation growth represents the true induced frequency. The detection of freshly-induced mutants seemed to depend upon the dilution and decay of products formed from the genes prior to their mutation by radiation, since (a) selection of mutants in a higher concentration of thioguanine (2 μ g/ml) increased the post-irradiation growth interval required to detect the maximum frequency of induced mutants, and (b) with increasing duration of post-irradiation growth in the non-selective medium, induced mutant cells were able progressively to overcome the growth-limiting effects of the analogue, to give rise to large colonies when respread in thioguanine-medium. The radiosensitivities of 7 isolated mutant lines were indistinguishable from that of wild type cells, but the mutants were at a slight disadvantage when grown in competition with wild type cells. This disadvantage was consistent with the expected fitness of mutants relative to wild type cells calculated from estimates of the spontaneous mutation rate and the mean spontaneous mutation frequency. The induction of mutation to thioguanine resistance was non-linear with dose, yielding induced frequencies per rad of 5 · 10 −8 to 3 · 10 −7 , but a plot of induced mutation frequency against log surviving fraction gave an approximately linear relationship. The same linear relationship holds for recently-published data on human and mouse cell cultures, so that all three mammalian cell types exhibit the same fixed probability of mutation induction relative to the extent of inactivation caused by ionising radiation.

The induction of thioguanine-resistant mutants of Chinese hamster cells by γ-rays

SummaryA versatile irradiator has been constructed for in vitro irradiation of mammalian cells with α-particles of well-defined energy, LET, direction, dose and dose rate. It is based on ∼ 1·2 × 109 Bq of 238Pu (on a platinum disc) contained in a He-filled chamber. In a standard configuration, monolayers of cells grown in 10 Hostaphan-based dishes are irradiated with 3·26 ± 0·22 MeV α-particles (LET 121 keV μm−1) at selectable dose rates from ∼ 2 Gy min−1 down to < 10−4 Gy min−1 (i.e. fluence rates of 1 × 107 cm−2 min−1 to 3 × 102 cm−2 min−1). Single dishes can be irradiated at dose rates up to 24 Gy min−1 (fluence rate 1 × 108 cm−2 min−1). Incident energy and LET can be varied from 0·8 to 4·2 MeV and 266 to 102 keV μm−1, respectively. The irradiator has full incubation and gassing facilities for protracted irradiations. The irradiator is particularly suitable for in vitro analytical studies of the biological effects of α-particles of energies and LETs similar to those which cells may receive in vivo from...

A versatile plutonium-238 irradiator for radiobiological studies with alpha-particles.

Four X-ray-sensitive mutants of CHO cells, described previously by Jeggo and Kemp (1983), showed enhanced sensitivity to both 60 Co γ-rays and 238 Pu α-particles relative to the responses of the parent line. The enhanced response to a densely ionising radiation (α-particles) was less than that to X- or γ-rays, suggesting that these mutants are deficient mainly in the repair of damage from relatively sparsely ionising radiation tracks. Plateau-phase cultures of the parental CHO cells showed considerable recovery upon irradiation with low-dose-rate γ-rays, compared to irradiation at ‘high’ dose rates, but little or no recovery was seen for the mutants. Similarly, preliminary data on recovery during post-irradiation holding of plateau-phase cultures show that this process is also absent in the mutants. These responses have several similarities to those of cells from patients with the radiosensitive disorder ataxia telangiectasia (AT), and are discussed with reference to AT cells and other radiosensitive mutants.

Albert Stretch

Papers

Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions. II. Chinese hamster V79 cells.

Direct comparison between protons and alpha-particles of the same LET: I. Irradiation methods and inactivation of asynchronous V79, HeLa and C3H 10T1/2 cells.

The induction of thioguanine-resistant mutants of Chinese hamster cells by γ-rays

A versatile plutonium-238 irradiator for radiobiological studies with alpha-particles.

Responses of 4 X-ray-sensitive CHO cell mutants to different radiations and to irradiation conditions promoting cellular recovery.