Showing papers in "International Journal of Radiation Biology in 1985"
TL;DR: The IR model of survival after fractionated or continuous irradiation is compared to the 'lethal, potentially lethal' (LPL) model after the latter has been generalized to an arbitrary number of fractions and to low dose-rate, continuous exposures and it is shown that the two models are equivalent.
Abstract: An incomplete-repair (IR) model of survival after fractionated or continuous irradiation is derived from the concept of ‘dose-equivalent’ of incomplete repair. The model gives reasonably good predi...
473 citations
TL;DR: The neutral filter elution technique has been used and it is concluded that DNA dsb is probably the lethal lesion induced by ionizing radiation.
Abstract: SummaryThe neutral filter elution technique has been used to examine the relationship between X-ray-induced DNA double-strand breakage (dsb) and lethal lesions. The ratios of the different lesions produced by X-irradiation were varied by irradiation in the presence of different radiomodifiers, and in each case the same linear relationship between lethal lesions and induced DNA dsb was found. This relationship also held for cells given a hyperthermic treatment before irradiation. It is concluded that DNA dsb is probably the lethal lesion induced by ionizing radiation.
322 citations
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307 citations
TL;DR: X-ray-induced DNA double-strand breakage and lethal lesion induction have been examined using normal and transformed fibroblasts of rodent and human origin and linear relationships were found, suggesting a comparable probability of conversion of DNA dsb into a lethal lesions.
Abstract: SummaryX-ray-induced DNA double-strand breakage (dsb) and lethal lesion induction have been examined using normal and transformed fibroblasts of rodent and human origin. DNA dsb induction varied markedly among the different cell types and was found to reflect radiosensitivity. Linear relationships were found between DNA dsb and lethal lesion induction which were not significantly different for each cell type, suggesting a comparable probability of conversion of DNA dsb into a lethal lesion. The implications of these findings for models of cell survival are discussed.
281 citations
TL;DR: Phthalocyanines, porphyrin-like compounds with maximum absorption in the red, which were previously reported to localize selectively in tumours, have been shown to be efficient photosensitizers of mammalian cells in culture, thus making them possible candidates to replace haematopomorphyrin derivatives in cancer phototherapy.
Abstract: SummaryPhthalocyanines, porphyrin-like compounds with maximum absorption in the red, which were previously reported to localize selectively in tumours, have been shown to be efficient photosensitizers of mammalian cells in culture, thus making them possible candidates to replace haematoporphyrin derivatives in cancer phototherapy.
192 citations
TL;DR: The yield of hydrogen peroxide in the sonication of argon-saturated water was studied in the presence of various solutes and the efficiency of OH radical scavenging is expressed by the reciprocal value of C 1/2, the solute concentration at which the H2O2 yield is decreased by 50 per cent.
Abstract: SummaryThe yield of hydrogen peroxide in the sonication of argon-saturated water was studied in the presence of various solutes. The efficiency of OH radical scavenging is expressed by the reciprocal value of c½, the solute concentration at which the H2O2 yield is decreased by 50 per cent. c½ ranges over several orders of magnitude. It is not related to the specific reactivity towards OH in homogeneous solution. However, it is correlated to the hydrophobicity of the solutes. The competition of I− and a second solute for OH was also studied. The competition between I− and HCO−2 follows similar kinetics as in homogeneous solution. However, many other solutes compete in the manner which would be expected if radical scavenging occurred in different phases. The effects are explained in terms of OH radical formation in gaseous argon bubbles, combination of OH radicals to form H2O2 in an interfacial area, and enrichment of hydrophobic solutes in the bubbles.
189 citations
TL;DR: This survey focuses on recent developments in the radiation chemistry of purine bases in nucleic acids and related model compounds with special emphasis on the structural characterization of the final decomposition products of nucleic acid components.
Abstract: SummaryThis survey focuses on recent developments in the radiation chemistry of purine bases in nucleic acids and related model compounds. Both direct and indirect effects of ionizing radiation are investigated with special emphasis on the structural characterization of the final decomposition products of nucleic acid components. Available assays for monitoring radiation-induced base lesions are critically reviewed.
179 citations
TL;DR: Addition of alkaline phosphatase and WR-2721 to culture medium containing V79-171 cells leads to production of WR-1065 and its disulphide forms in the medium, and to radioprotection which correlates with cellular WR- 1065 level.
Abstract: Addition of alkaline phosphatase and WR-2721 to culture medium containing V79-171 cells leads to production of WR-1065 and its disulphide forms in the medium, to cellular accumulation of WR-1065, and to radioprotection which correlates with cellular WR-1065 level.
168 citations
TL;DR: It seems that the effects of membrane fluidity on cell responses to hyperthermia and radiation are due to an indirect influence on functional membrane proteins, and the major role of lipid peroxidation in radiation damage to membranes has been questioned.
Abstract: Results of numerous studies demonstrate that membranes are important sites of cell damage by both ionizing radiation and hyperthermia. Modification of membrane properties (mainly lipid fluidity) af...
163 citations
TL;DR: The results reported here show that Pvu II simulates X-ray exposure, in causing a dose-dependent loss of the reproductive integrity of mammalian cells, and support the notion that X-irradiated mammalian cells undergo a mode of death in which dsb in the DNA cause chromosomal aberrations which are lethal as a result of loss of genetic material in the form of chromosome fragments, or as the result of chromosome bridge formation.
Abstract: Permeabilized Chinese hamster cells were treated with the restriction endonucleases Pvu II and Bam H1 which generate blunt-ended and cohesive-ended DNA double-strand breaks (dsb), respectively. Cells were then assayed for their clonogenic ability. These experiments were performed to test the hypothesis that mammalian cell death following X-ray exposure arises from the induction of dsb in DNA, and via the formation of chromosomal aberrations. It was shown previously that Pvu II induces chromosome aberrations whereas Bam H1 was ineffective in this respect. The results reported here show that Pvu II simulates X-ray exposure, in causing a dose-dependent loss of the reproductive integrity of mammalian cells. Dsb generated by Pvu II, i.e. with blunt ends, can therefore be regarded as potentially clastogenic as well as potentially lethal. Bam H1 was found not to reduce cell survival in the same enzyme dose range. These results support the notion that X-irradiated mammalian cells undergo a mode of death in which dsb in the DNA cause chromosomal aberrations which are lethal as a result of loss of genetic material in the form of chromosome fragments, or as a result of chromosome bridge formation.
149 citations
TL;DR: It is concluded that O2- is involved very little, if at all, in the phthalocyanine-induced photo-killing of mammalian cells.
Abstract: SummaryThe effect of the central metal atom on the photodynamic activity of phthalocyanine dyes has been estimated by cytotoxicity to cultured Chinese hamster cells. Chloroaluminium phthalocyanine, followed by the Zn- derivate, were found to be the only active dyes. In parallel it was found that visible light (615 ± 10 nm) excitation of phthalocyanines dissolved in dimethylsulphoxide in the presence of oxygen generates superoxide radical anion. O−2 radicals were spintrapped with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) and identified by electron spin resonance. The quantum yields for O−2 generation range from 10−5 (Zn-phthalocyanine) to 4·2 × 10−4 (Ga-phthalocyanine). The efficiency of generating O−2 was apparently uncorrelated with the phototoxicity of the same dyes. Furthermore, the biological photodamage could not be inhibited by the addition of superoxide dismutase. It is concluded that O−2 is involved very little, if at all, in the phthalocyanine-induced photo-killing of mammalian cells.
TL;DR: The one-electron oxidation of dGMP (dG) by Br-.2 was shown to result in the formation of a species, the properties of which are similar to those of the OH-radical adduct ofdGMP with oxidizing properties based upon both spectral and kinetic information.
Abstract: Using the technique of pulse radiolysis, it has been demonstrated that the interaction of hydroxyl-radical adducts of dG and dGMP with a series of reductants with different oxidation potentials at pH 7.0-7.4 proceeds via an electron transfer process (k approximately 1.4-34 X 10(8) dm3 mol-1s-1). The one-electron oxidation of dGMP (dG) by Br-.2 was shown to result in the formation of a species, the properties of which are similar to those of the OH-radical adduct of dGMP with oxidizing properties based upon both spectral and kinetic information. The nature of the dGMP species produced on interaction with Br-.2 is discussed in terms of the ability of Br-.2 to produce specific base damage. The implications of these findings are presented in terms of potential free radical repair of hydroxyl radical damage and of synergistic effects whereby one reductant may be regenerated at the expense of another reductant.
TL;DR: Modelling shows that this might be consistent with a sub-population of the cells showing an exceptional radiosensitivity, and a replenishment of this subpopulation occurring in the 8 h between small dose fractions, and more experiments are needed in order to confirm this hypothesis for skin and for other tissues.
Abstract: The partial tolerance type of 'top-up' experiment has been investigated to determine the resolution of this approach for studying the damage to mouse skin from very small doses of X-rays and neutrons. The effect of 20 fractions, each as small as 0.10 Gy of X-rays or of 0.05 Gy of neutrons, can be detected if 3 MeV neutrons are used as the 'top-up' reference radiation. This capability results from the almost linear underlying dose-response curve and highly reproducible dose-effect relationship for the low energy neutrons. The data fit the linear quadratic model of dose fractionation for X-rays down to fractional doses of 0.75 Gy, but at lower doses there is a trend towards an increase in the skin radiosensitivity. Modelling shows that this might be consistent with a sub-population of the cells showing an exceptional radiosensitivity, and a replenishment of this subpopulation occurring in the 8 h between small dose fractions. More experiments are needed at very low doses in order to confirm this hypothesis for skin and for other tissues.
TL;DR: The neutral filter elution assay, for measurement of DNA double strand breakage, has been calibrated using mouse L cells and Chinese hamster V79 cells labelled with [125I]dUrd and then held at liquid nitrogen temperature to accumulate decays.
Abstract: SummaryThe neutral filter elution assay, for measurement of DNA double strand breakage, has been calibrated using mouse L cells and Chinese hamster V79 cells labelled with [125I]dUrd and then held at liquid nitrogen temperature to accumulate decays. The basis of the calibration is the observation that each 125I decay, occurring the DNA, produces a DNA double strand break. Linear relationships between 125I decays per cell and lethal lesions per cell (minus natural logarithm survival) and the level of elution, were found. Using the calibration data, it was calculated that the yield of DNA double strand breaks after X-irradiation of both cell types was from 6 to 9 × 10−12 DNA double strand breaks per Gy per dalton of DNA, for doses greater than 6 Gy. Neutral filter elution and survival data for X-irradiated and 125I-labelled cells suggested that the relationships between lethal lesions and DNA double strand breakage were significantly different for both cell types. An attempt was made to study the repair kin...
TL;DR: Average intracellular concentrations of five radiosensitizers in hamster fibroblast-like V79-379A cells in vitro were measured by high performance liquid chromatography, varying the extracellular pH (pHe) and estimating the apparent intrACEllular pH from the distribution of 5,5-dimethyloxazolidine-2,4-dione.
Abstract: SummaryAverage intracellular concentrations of five radiosensitizers in hamster fibroblast-like V79-379A cells in vitro were measured by high performance liquid chromatography, varying the extracellular pH (pHe) and estimating the apparent intracellular pH from the distribution of 5,5-dimethyloxazolidine-2,4-dione. The intracellular: extracellular concentration ratio for the 2-nitroimidazole, misonidazole was constant at about 0·7 for pHe = 6·6–7·6, whereas the weak base, Ro 03-8799 (1-(2-nitro-1-imidazolyl)-3-N-piperidino-2-propanol) was concentrated intracellularly at pHe = 7·3–7·4 by a factor of 3·3, the factor increasing from about 0·8 at pHe = 6·0, to 7·5 at pHe = 7·85. The weak acid, azomycin (2-nitroimidazole) showed approximately constant uptake (factor 1·1) between pHe = 6·0–7·0, decreasing to 0·8 at pHe = 7·3 and 0·4 at pHe = 7·8. Measurements of intracellular uptake of Ro 31-0052 (the more hydrophilic and less basic 3′-hydroxypiperidino analogue of Ro 03-8799) and of Ro 31-0258 (3-(2-nitro-1-im...
TL;DR: The target size for inhibition of DNA replicon initiation is so large that it must include many replicons, which is consistent with the concept that a single lesion anywhere within a large group (cluster) of replicons is sufficient to block the initiation of replication of all replicons within that cluster.
Abstract: A semi-log plot of the inhibitory effect of ionizing radiation on the rate of DNA synthesis in normal mammalian cells yields a two-component curve. The steep component, at low doses, has a D0 of about 5 Gy and is the result of blocks to initiation of DNA replicons. The shallow component, at high doses, has a D0 of greater than or equal to 100 Gy and is the result of blocks to DNA chain elongation. The target size for the inhibition of DNA replicon initiation is about 1000 kb, and the target size for inhibition of DNA chain elongation is about 50 kb. There is evidence that the target for both components is DNA alone. Therefore, the target size for inhibition of DNA chain elongation is consistent with the idea that an effective radiation-induced lesion in front of the DNA growing point somehow blocks its advance. The target size for inhibition of DNA replicon initiation is so large that it must include many replicons, which is consistent with the concept that a single lesion anywhere within a large group (cluster) of replicons is sufficient to block the initiation of replication of all replicons within that cluster. Studies with radiosensitive human cell mutants suggest that there is an intermediary factor whose normal function is necessary for radiation-induced lesions to cause the inhibition of replicon initiation in clusters and to block chain elongation; this factor is not related to poly(ADP-ribose) synthesis. Studies with radiosensitive Chinese hamster cell mutants suggest that double-strand breaks and their repair are important in regulating the duration of radiation-induced inhibition of replicon initiation but have little to do with effects on chain elongation. There is no simple correlation between inhibition of DNA synthesis and cell killing by ionizing radiation.
TL;DR: The ideal platinum drug-radiation interaction would achieve radiosensitization of hypoxic tumour cells with the use of a dose of drug which is completely non-toxic to normal tissues, but the commoner platinum drugs are only weakly electron-affinic, so the amount of enhancement will vary with both the platinum drug dose and the time interval between drug administration and radiation.
Abstract: Platinum drugs have chemical as well as biochemical and biological effects on cells, all of which may interact with radiation effects. They inhibit recovery from sublethal and potentially lethal radiation damage. They produce a pattern of chromosome aberrations analogous to that from alkylating agents. Cellular sensitivity to platinum is increased when glutathione levels are reduced, just as is radiosensitivity. There is a pattern of drug sensitivity throughout the phases of the cell cycle which is different from that for radiosensitivity. The ideal platinum drug-radiation interaction would achieve radiosensitization of hypoxic tumour cells with the use of a dose of drug which is completely non-toxic to normal tissues. Electron-affinic agents are employed with this aim, but the commoner platinum drugs are only weakly electron-affinic. They do have a quasi-alkylating action however, and this DNA targeting may account for the radiosensitizing effect which occurs with both pre- and post-radiation treatments. Because toxic drug dosage is usually required for this, the evidence of the biological responses to the drug and to the radiation, as well as to the combination, requires critical analysis before any claim of true enhancement, rather than simple additivity, can be accepted. The amount of enhancement will vary with both the platinum drug dose and the time interval between drug administration and radiation. Clinical schedules may produce an increase in tumour response and/or morbidity, depending upon such dose and time relationships.
TL;DR: Exchange aberrations require recombination between two separate chromosomes, but they are induced efficiently by carbon X-rays with a substantial linear component to the dose-response despite the very short electron tracks that they produce in the cell.
Abstract: SummaryV79 hamster cells in plateau (extended G1) phase were irradiated with either 250 kV (‘hard’) X-rays or carbon K characteristic ultrasoft X-rays under conditions minimizing cell overlap. These cells were killed most effectively by the carbon X-rays, by a factor of about 3 relative to hard X-rays, in agreement with our previous findings with cells in exponential growth. Chromosome-type aberrations were measured at 3 fixation times within the first division cycle after irradiation, and an approximately uniform sensitivity to aberration induction was found for both radiations. The combined aberration data show that carbon X-rays are 2 or more times as effective as hard X-rays, depending on dose and/or data fit. Exchange aberrations require recombination between two separate chromosomes, but they are induced efficiently by carbon X-rays with a substantial linear component to the dose-response despite the very short electron tracks (≲≲ 7 nm) that they produce in the cell. This implies either that the par...
TL;DR: The plot of the reciprocal of the LD50 values as a function of dose per fraction was non-linear, suggesting that a linear quadratic dose response model may not be appropriate or that repair of cellular injury in lung is not complete in 3 h, or both.
Abstract: The response of mouse lung to repeated doses of 60 Co n -rays of as low as 115 cGy per fraction was measured using death from pneumonitis between 80 and 120 days after irradiation as the endpoint. A fractionation interval of 3 h was maintained for most regimens but in the longer experiments some 12 h intervals were introduced for logistic reasons. The longest overall duration (for a 43 fraction regimen) was 8 days. The total doses required to produce 50 per cent mortality increased continuously as dose/fraction was decreased, even from 160 to 115 cGy per fraction. Of clinical relevance, the steepness of the isoeffect curve over the dose range 115-500 cGy indicates that the lung shows greater sparing from dose fractionation than is characteristic of more rapidly-responding normal tissues, resembling, in this respect, other more slowly-responding tissues such as spinal cord. The plot of the reciprocal of the LD 50 values as a function of dose per fraction was non-linear, suggesting that a linear quadrat...
TL;DR: It is concluded that photoionization of the uracil moiety in poly U leads eventually to the same chemical pathway for ssb formation as that induced by OH radicals and proposed that protection by DTT and GSH occurs via H donation to the C-4' radicals of the sugar moiety of DNA.
Abstract: SummaryLaser flash photolysis of polyuridylic acid (poly U) in anoxic aqueous solutions leads to biphotonic photoionization of the uracil moiety followed by the formation of single strand breaks (ssb). The rate constant for ssb formation (1·0 s−1, obtained from the slow component of conductivity increase at 23°C and pH 6·8) increases with decreasing pH to 235 s−1 at pH 3·5. The activation energy (pre-exponential factor) was measured to be 66 kJ mol−1 (5 × 1011 s−1) at pH 6·8. Addition of dithiothreitol (DTT) or glutathione (GSH) prevents ssb formation by reacting with a poly U intermediate (rate constant = 1·2 × 106 and 0·16 × 106 dm3 mol−1 s−1, respectively). Since with OH radicals as initiators very similar data have been obtained for the kinetics of ssb formation and for the reaction with DTT, we conclude that photoionization of the uracil moiety in poly U leads eventually to the same chemical pathway for ssb formation as that induced by OH radicals. Furthermore, we propose that protection by DTT and G...
TL;DR: It is shown that with very heavy ions the biological effectiveness is no longer unambiguously related to a single parameter like l.e.t. or Z*2/beta 2 but depends strongly on ion energy, pointing to the importance of far-reaching delta-electrons.
Abstract: The biological effects of irradiation with ions of masses larger than 40 and energies up to 20 MeV per atomic mass unit are reviewed. The objects are viruses, bacterial spores, yeast and mammalian cells. Experimental parameters include loss of colony forming ability, induction of mutants, chromosomal aberrations, cell cycle progression, inhibition of biochemical activities and the formation of strand breaks. Some of the pertinent physical questions--e.g. track structure--are also discussed. It is shown that with very heavy ions the biological effectiveness is no longer unambiguously related to a single parameter like l.e.t. or Z*2/beta 2 but depends strongly on ion energy. This points to the importance of far-reaching delta-electrons. The analysis indicates also that even with very high l.e.t., cells are not killed by the passage of a single particle through their nucleus. Possible implications of the findings for fundamental radiation biology are outlined.
TL;DR: The effect of three radiomodifying agents, cysteamine, hyperthermia, and hypoxia, on the induction of the major classes of X-ray-induced DNA lesions support the previous suggestion that the X- Ray-induced lethal lesion is DNA double-strand breakage.
Abstract: SummaryThe effect of three radiomodifying agents, cysteamine, hyperthermia, and hypoxia, on the induction of the major classes of X-ray-induced DNA lesions, was studied using mouse L cells and Chinese hamster V79 cells. The use of filter elution techniques allowed most of these studies to be conducted at X-ray doses within the survival-curve range. Cysteamine was found to protect against DNA single-strand breakage (ssb), DNA base damage, and DNA-protein crosslinkage. Hyperthermia had no effect on the level of DNA ssb or DNA base damage, but in L cells (but not in V79 cells) it increased the level of DNA-protein crosslinkage relative to DNA ssb. Hypoxia protected against DNA ssb, had no significant effect on the level of DNA base damage, and enhanced the level of DNA-protein crosslinkage relative to DNA ssb. These results support the previous suggestion that the X-ray-induced lethal lesion is DNA double-strand breakage. Implications of these findings for the mechanisms of formation of X-ray-induced DNA les...
TL;DR: The results were interpreted to indicate that glutathione plays a role in both the radical and the biochemical reactions which follow irradiation, in general agreement with the 'competition model'.
Abstract: Observations are reviewed from experiments performed to study the role of endogenous thiols in the radiation response of cells using a glutathione-deficient and a related glutathione-proficient cell strain. The effect of glutathione in the initial radical reactions was considered and the yield of single-strand DNA breaks was the end-point of the response. The rejoining of breaks and clonogenic survival were chosen as end-points when, in addition, the role of glutathione in the subsequent biochemical processes was studied. The results were interpreted to indicate that glutathione plays a role in both the radical and the biochemical reactions which follow irradiation. In the former case, it functions as a damage-restituting reactant, in general agreement with the 'competition model'. Some biochemical repair processes, in particular those concerned with the rejoining of breaks induced by radiation in the presence of oxygen or misonidazole, appear also to be critically dependent on glutathione. Due, probably,...
TL;DR: Ataxia-telangiectasia (A-T) cells are hypersensitive to the lethal effects of ionizing radiation and fail to inhibit DNA synthesis following radiation exposure, but the kinetics of DNA synthesis after gamma-irradiation are similar to those of A-T cells.
Abstract: Ataxia-telangiectasia (A-T) cells are hypersensitive to the lethal effects of ionizing radiation and fail to inhibit DNA synthesis following radiation exposure. A cell line derived from an A-T line following DNA-mediated gene transfer has normal radiation sensitivity, but the kinetics of DNA synthesis after gamma-irradiation are similar to those of A-T cells.
TL;DR: Although the activity of the cellular DNA polymerases was related to cell survival after single heat doses, no correlation was found when thermotolerant cells were heated, and it is concluded that (the nuclear bound)DNA polymerases are not to be considered as key enzymes in cellular heat sensitivity of HeLa S3 cells.
Abstract: SummaryThe activity of DNA polymerase α and β was assayed in heated HeLa S3 cells as well as in nuclei isolated from these cells. The enzyme activity as measured in cells and in nuclei has been compared with the extent of cell survival after the different hyperthermic doses. It was found that although the activity of the cellular DNA polymerases was related to cell survival after single heat doses, no correlation was found when thermotolerant cells were heated. When the activity of the DNA polymerases was determined in nuclei isolated from non-heated and heated cells, more polymerase activity was found in the nuclei of the heated cells. However, the heat sensitivity of DNA polymerase activity was the same for nuclei isolated from control, pre-heated and thermotolerant cells. Heat protection of polymerase activity by erythritol and sensitization by procaine was found when cells, but not when nuclei, were heated in the presence of these modifiers. It is concluded that (the nuclear bound) DNA polymerases are...
TL;DR: In this paper, the induction of thyroid cancer by ionizing radiation was discussed, and it was shown that thyroid cancer can be prevented by using ionising radiation in the thyroid gland.
Abstract: (1985). Induction of Thyroid Cancer by Ionizing Radiation. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine: Vol. 49, No. 1, pp. 193-194.
TL;DR: To determine the yield of radiation-induced single-strand, double-Strand and potential breaks (breaks which are converted into actual breaks by alkali or heat treatment) oxygenated aqueous solutions of phi X174 supercoiled circular double-stranded DNA were irradiated with increasing doses of gamma-irradiation and subjected to electrophoresis on agarose gels both before and after heat treatment.
Abstract: To determine the yield of radiation-induced single-strand, double-strand and potential breaks (breaks which are converted into actual breaks by alkali or heat treatment) oxygenated aqueous solutions of phi X174 supercoiled circular double-stranded (RFI) DNA were irradiated with increasing doses of gamma-irradiation and subjected to electrophoresis on agarose gels both before and after heat treatment. A complete separation was obtained of RFI, RFII (relaxed circle due to one or more single-strand breaks) and RFIII (linear DNA due to one double-strand break). A computer-assisted spectrophotometric procedure was developed, which enabled us to measure very accurately the amount of DNA present in the three DNA fractions. The quantitative changes of each fraction of DNA with dose could be fitted to a straightforward statistical model, which described the dose-dependent formation of the different types of breaks and from which the D37-values of single-strand, potential single-strand and double-strand breaks could be calculated to be 0.42 +/- 0.02, 1.40 +/- 0.25 and 57 +/- 36 Gy respectively. Potential double-strand breaks were not formed significantly under our conditions. In addition the maximum distance between two independently introduced single-strand breaks in opposite strands resulting in a double-strand break could be determined. The values before and after heat treatment are shown to be 29 +/- 6 and 102 +/- 13 nucleotides, respectively.
TL;DR: There is a predictable diminution of the OH mediated effect with increasing LET infinity; however, the biological effect cannot be predicted accurately from calculated LET infinity values for high energy particle irradiation, nor indeed from a variety of low energy charged particles of quite different energies (incident velocities).
Abstract: SummaryThe extent of hydroxyl radical mediated cell inactivation was measured for a variety of particle beams ranging from 8·5 MeV/u neon ions to 570 MeV/u argon ions. In general, the fraction of the total radiosensitivity caused by OH· decreases from close to 60 per cent at low ionization density or low linear energy transfer (low LET) to close to 25 per cent at high LET for aerobically irradiated mammalian cells. The extent of OH· induced cell lethality can be explained in terms of LET∞ only for low energy or low atomic number particles where fragmentations and complicated track structures do not contaminate the characteristic particle LET. For example, at a calculated LET∞ of 100 keV/μm, the OH· mediated fraction of the total radiation damage is about 25 per cent for low energy carbon but close to 40 per cent for high energy carbon ions. For low energy charged nuclei of approximately the same energy, as the 5·4–13·4 MeV/u He, Li, C and Ne ions in this report, there is a predictable diminution of the OH...