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D T Goodhead

Publications and source records attributed to D T Goodhead.

At least 73 records · Page 4Linked to original sources
PubMed1992

Direct comparison of biological effectiveness of protons and alpha-particles of the same LET. III. Initial yield of DNA double-strand breaks in V79 cells.

The results reported form part of a series of experiments to substantiate and extend the findings by Belli et al. (1989) that protons are more biologically effective at cell killing than alpha-particles of the same LET. The irradiations were carried out using the Variable Energy Cyclotron (VEC) at the Harwell Laboratories. V79-4 Chinese hamster cells were exposed to alpha-particles and protons with LETs of 20 and 23 keV microns-1 in the dose range 40-150 Gy. X-rays were also used for comparison. Two methods were used for measurement of initial DNA double-strand breaks: sedimentation and DNA precipitation assays. The dose-response relationships were found to be well fitted by straight lines in all cases. With the sedimentation assay a slightly lower yield of dsb was found from protons than from alpha-particles of the same LET. The yield from X-rays was not significantly different from either. The precipitation assay showed similar yields of DNA damage from both particle types but significantly higher yields from X-rays. This may reflect a difference in the type of lesions scored by the two methods. Since the initial amount of dsb does not account for the observed differences in cellular response to radiations of different qualities, it is likely that these are related to the nature of the dsb (affecting reparability) or to the occurrence of other types of molecular damage.

Alpha Particles↗
PubMed1991

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

A versatile irradiator has been constructed for in vitro irradiation of mammalian cells with alpha-particles of well-defined energy, LET, direction, dose and dose rate. It is based on approximately 1.2 x 10(9) 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 alpha-particles (LET 121 keV microns-1) at selectable dose rates from approximately 2 Gy min-1 down to less than 10(-4) Gy min-1 (i.e. fluence rates of 1 x 10(7) cm-2 min-1 to 3 x 10(2) cm-2 min-1). Single dishes can be irradiated at dose rates up to 24 Gy min-1 (fluence rate 1 x 10(8) cm-2 min-1). Incident energy and LET can be varied from 0.8 to 4.2 MeV and 266 to 102 keV microns-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 alpha-particles of energies and LETs similar to those which cells may receive in vivo from radionuclides such as radon and the actinides. It has been used successfully for investigations of a variety of alpha-particle-induced effects in different cell types irradiated either as attached monolayers or as very thin suspensions.

Alpha Particles↗
PubMed1991

Energy deposition in small cylindrical targets by monoenergetic electrons.

Calculations of energy deposition in cylindrical target volumes of diameter and height 1-100 nm, including those similar to the dimensions of biological molecules and structures such as DNA, nucleosomes and chromatin fibre, have been made. The calculations used the Monte Carlo track structure program MOCA8B for electrons of initial energy 0.1-100 keV. Details of the calculation are presented, as well as a selection of results. The frequency distributions of energy deposition events per gray per target, placed at random in a homogeneous aqueous medium, are given for uniform irradiation with monoenergetic electrons of various energies. The frequency distributions have been used to predict the initial biophysical parameters such as relative effectiveness for initial damage. These suggest that the final biological effects which depend on complex local damage may show substantial variations in biological effectiveness for different low linear energy transfer radiations, whereas those that depend on simple local damage may not.

Chromatin↗
PubMed1991

Track structure analysis illustrating the prominent role of low-energy electrons in radiobiological effects of low-LET radiations.

Monte Carlo track structure methods have been used to illustrate the importance of low-energy electrons produced by low-LET radiations. It is shown that these low-energy secondary electrons contribute substantially to the dose in all low-LET irradiations and are particularly efficient at producing highly localized clusters of atomic damage which may be responsible for a major part of the biological effectiveness of low-LET radiations. The data generated by Monte Carlo track structure techniques and by earlier semi-analytical methods based on the LET concept have been compared in terms of cumulative and differential fractions of total dose absorbed as a function of electron energy. The data show that low-energy secondary electrons account for up to nearly 50% of the total dose imparted to a medium when irradiated with electrons or photons.

Electrons↗
PubMed1990

Thickness measurements on V79-4 cells: a comparison between laser scanning confocal microscopy and electron microscopy.

A quantitative comparison has been carried out between laser scanning confocal microscopy on living cells and standard electron microscope methods on fixed samples. It was estimated from these measurements that there was about 10-20% reduction in thickness in fixed samples of monolayer V79-4 hamster cells. Precise information on the true thickness of living cells, as irradiated, is required for full interpretation of radiobiological data with poorly penetrating radiations, including ultrasoft X-rays. The confocal microscope allows rapid measurements on unperturbed living samples.

Animals↗
PubMed1989

Production of chromosome aberrations, micronuclei, and sister-chromatid exchanges by 24-keV epithermal neutrons in human G0 lymphocytes.

The induction of chromosome aberrations, micronuclei and sister-chromatid exchanges in human G0 lymphocytes by 24-keV epithermal neutrons has been measured. Positive linear dose responses were obtained for the 3 end points, with a tendency to saturation at higher dose for SCE production. In all cases, the responses to 24-keV neutrons were characteristic of high-LET radiations.

Chromosome Aberrations↗
PubMed1989

Breakage of human interphase chromosomes by alpha particles and X-rays.

The technique of premature chromosome condensation (PCC) was used to compare the early formation of chromosome breaks in non-cycling HF19 human diploid fibroblasts when irradiated with slow alpha particles (3.2 MeV, 128 keV micron-1) or 250 kVP X-rays. For both radiations the production of PCC breaks increased approximately linearly with dose. The production coefficient for alpha particles was 12.5 +/- 0.6 per cent per Gy and for X-rays it was 5.8 +/- 0.2 per cell per Gy. Hence, the relative biological effectiveness (RBE) of the alpha particles was 2.16 +/- 0.13. This is smaller than reported values of the RBE for the production of chromosome-type exchange aberrations by slow alpha particles. This implies that there is a difference, spatial or qualitative, in the initial breaks produced by the densely ionizing alpha particle tracks and the more sparsely ionizing electron tracks from the X-rays.

Alpha Particles↗
PubMed1989

Track structure analysis of ultrasoft X-rays compared to high- and low-LET radiations.

Monte-Carlo track structure simulations of ultrasoft X-rays, and of selected low- and high-LET radiations for comparison, have been used to obtain statistically valid frequency distributions of energy deposition in small subcellular targets which resemble the dimensions of short segments of DNA, nucleosomes and short segments of chromatin fibre. It is found that in all cases large numbers (approximately 10(3] of direct energy deposition events occur in these targets in a single mammalian cell irradiated with 1 Gy of any of these radiations. In almost all cases the numbers of energy depositions of substantial size (say, approximately greater than 100 eV in a DNA segment, approximately greater than 300 eV in a nucleosome or approximately greater than 800 eV in a segment of chromatin fibre) are also quite large, being approximately 10 to 100 per cell per Gy. It seems clear therefore that the direct effects of radiation on macromolecules must be considered in assessing the biological effects of any ionizing radiations on mammalian cells. The calculations also show that high-LET radiations can produce uniquely large energy depositions in the targets, such as are virtually unachievable by any of the other radiations; this allows the possibility of unique biochemical and cellular damage by high-LET radiations. At any realistic dose for mammalian cells, virtually all the energy depositions in these targets, from all the radiations, are due to single independent tracks; the multi-track component is negligibly small. The absolute numbers of energy depositions of approximately greater than 100 eV in DNA segments in a cell are similar to experimentally measured numbers of DNA double-strand breaks, but both these sets of numbers are one or two orders of magnitude larger than the numbers of lethal events produced in mammalian cells. The frequency of threshold energy of approximately 120 eV in a DNA segment correlates reasonably well with the relative biological effectiveness of ultrasoft X-rays and low-LET radiations for relatively radioresistant cells, but a lower threshold energy may be required for other, more sensitive, cells.

Alpha Particles↗
PubMed1989

The initial physical damage produced by ionizing radiations.

Biophysical studies of different ionizing radiations and their differences in biological effect can provide useful information and constraints on the nature of the initial biologically relevant damage and hence the subsequent biochemistry and repair processes. It is clear that the nature of the predominant critical component produced by densely ionizing (high-LET) radiations is qualitatively, as well as quantitatively, different from that which predominates for low-LET radiations. Comparisons of radiation track structure with observed biological effects of the radiations allow hypotheses to be developed as to the nature of these different types of damage. That associated with low-LET radiations seems consistent with what is known about DNA double-strand breaks (dsb). It is produced predominantly by a localized cluster of ionizations within a single electron 'track end' either by direct action on the DNA or in conjunction with closely-associated molecules. The characteristic high-LET damage is somewhat larger in number of ionizations and spatial extent and therefore presumably also in molecular complexity. It is suggested that the total spectrum of initial damage be categorized into four classes; in addition to the above two this would include on the one extreme sparse isolated ionizations, which may lead to very simple products that are of limited biological relevance, and on the other extreme very large and relatively rare events which are uniquely achievable by some high-LET radiations, such as alpha-particles, but not at all by low-LET radiations. These biophysical considerations pose a challenge to radiation chemistry studies to consider the chemical consequences of highly localized clusters of initial ionizations and excitations in or very near to DNA, and to biochemistry to consider classes of damage involving DNA (and perhaps associated molecules) of greater complexity than the simplest dsb.

Cells↗
PubMed1989

Energy deposition in small cylindrical targets by ultrasoft x-rays.

A Monte Carlo technique has been employed to calculate the energy deposition events in small cylindrical targets (less than or equal to 100 nm), including sizes which represent the DNA duplex, nucleosome and chromatin fibre, by simulated electron tracks from C (278 eV), A1 (1487 eV) and Ti (4509 eV) characteristic ultrasoft x-rays in water. Detailed examples of input data tables for the generation of electron tracks produced from the x-ray photon interactions are presented. Frequencies of energy deposition events per gray for target sizes from 1 to 100 nm are given and comparisons have been made with radiations of different qualities.

Chromatin↗
PubMed1989

Radiobiology of ultrasoft X rays. II. Cultured C3H mouse cells (10T1/2).

In the first paper of this series (Radiat. Res. 110, 396-412 (1987], using V79 cells, we reported that the relative biological effectiveness (RBE) of ultrasoft X rays was found to increase with decreasing energy, and the oxygen enhancement ratio (OER) was found to decrease with decreasing energy. In this report, we present RBE and OER results for 10T1/2 cells that are known to grow uniformly flat and are considerably thinner than V79 cells. Thus the variation in dose across the cell nucleus is considerably reduced. The OER results agree well with our earlier V79 results. However, the RBE values for 10T1/2 cells compared to V79 cells are systematically less for all soft X rays and especially for 0.28 keV carbon-K (1.3 compared to 3.4 for V79 cells). Some plausible explanations are presented to reconcile the apparent discrepancy between V79 and 10T1/2 results.

Animals↗
PubMed1989

Radiobiology of ultrasoft X rays. III. Normal human fibroblasts and the significance of terminal track structure in cell inactivation.

Ultrasoft characteristic X rays from carbon (0.28 keV) are severely attenuated as they pass through biological material, causing a nonuniform distribution of dose to cell nuclei. Complications of studying ultrasoft X rays can be minimized in this context by using cells with very thin cytoplasm and nuclei (e.g., less than the attenuation length of the X rays), and which exhibit a more nearly exponential dose response to cell killing, such as normal human fibroblasts compared with V79 cells. Using this cell system, we report the relative biological effectiveness (RBE) of A1-K and C-K X rays to be near unity. Previous studies of cell inactivation by characteristic carbon X rays gave RBEs of 3 to 4, supporting the idea that localized energy depositions from secondary electrons and primary track ends represent the principal mode of biological action for other low-LET radiations. In part, the reported high RBEs result from the use of mean dose to describe energy deposited within the cell nuclei by these poorly penetrating radiations. Implicit in the use of mean dose is that cellular damage varies linearly with dose within a critical target(s), an assumption that is of questionable validity for cells that exhibit pronounced curvilinear dose responses. The simplest interpretation of the present findings is that most energy depositions caused by track-end effects are not necessarily more damaging than the sparsely ionizing component.

Cell Survival↗
PubMed1989

Radiobiology of ultrasoft X rays. IV. Flat and round-shaped hamster cells (CHO-10B, HS-23).

The results reported earlier in this series indicated that the relative biological effectiveness (RBE) of ultrasoft X rays decreases with decreasing cell thickness, approaching unity for the thinnest cells used, plateau-phase human skin fibroblasts (HSF). The possible dependence of RBE on the configuration of the cell nucleus is investigated further in this paper using two CHO cell lines that attach well and have similar intrinsic radiosensitivities to 60Co gamma rays. One of the lines forms monolayers similar to V79 cells, while the other remains more spherical during growth. We find an increasing RBE with decreasing X-ray energy for both of these cell lines, consistent with our results using V79 cells. Also consistent with our results obtained with 10T1/2 and HSF cells, we find an increasing RBE with increasing cell thickness. The possible dependence of RBE on radiosensitivity and the use of the concept of mean dose for ultrasoft X rays is discussed.

Animals↗
PubMed1988

Induction of sister chromatid exchanges (SCE) in G0 lymphocytes by plutonium-238 alpha-particles.

Irradiation of human G0 lymphocytes with plutonium-238 alpha-particles and X-rays was performed to investigate the production of sister chromatid exchanges (SCE). Alpha-particles produce a significant increase in SCE and this elevation is more significant when separated lymphocytes are irradiated. X-ray irradiation did not induce any significant increase in SCE. Therefore the relative biological effectiveness (RBE) for the induction of SCE by alpha-particles in this system is undefined and effectively infinite.

Alpha Particles↗
PubMed1988

Some optimum conditions for proton induced ultrasoft x-ray production.

The proton beam from an AN700 van de Graaff accelerator has been used to bombard solid targets of C, TiB2, SiC, SiN, Al and Au in the energy range 250-700 keV. A study of target surface contamination, the nature of the angular dependence in the x-ray emission and the dependence of the x-ray yield on proton energy has been undertaken. Our findings suggest that the optimum target angle is 30 degrees with respect to the incident proton direction and the detector angle 90 degrees to the target surface. In a vacuum of 10(-5) Torr (approximately 1.33 mPa) and at proton currents of 50-100 muA, a carbon deposit can be expected to build up with time on the target surface to reduce the characteristic x-ray intensity from the target. In the comparison between the energy dependent yields of CK and AlK x-rays, we find a slightly smaller dependence on energy than that predicted by the empirical cross section formula of Paul (1984) although the latter is not expected to be valid down to Z = 6.

Protons↗
PubMed1988

Spatial and temporal distribution of energy.

Studies of the spatial and temporal distribution of microscopic radiation doses lead to potentially important questions regarding conventional approaches to radiation protection. The short ranges of alpha-particle and Auger-electron emissions from radionuclides lead to uncertainties in assessing their hazards. The conventional extrapolations from intermediate doses to low doses and dose rates are questioned by observed dose-rate effects in the so-called "initial slope," by the total lack of data for single tracks in cells and by the possibility of multiple-cell effects. At all subcellular levels, even down to DNA, high linear-energy-transfer (LET) radiations can produce unique initial damage, different from that possible with low-LET radiations, and therefore may even, in principle, produce unique final biological effects. This questions simple extrapolations from low- to high-LET radiations and the application of universal quality factors to diverse effects. Further understanding of these questions could lead, in future, to substantial increases or decreases in estimations of risk.

Alpha Particles↗
PubMed1987

Physical mechanism for inactivation of metallo-enzymes by characteristic X-rays: analysis of the data of Jawad and Watt.

Table 1 summarizes the mean numbers of events and interactions of various types which we calculate to occur per single dihydro-orotic dehydrogenase enzyme when irradiated in solution with D37 = 99 Gy of 8.04 keV X-rays under the experimental conditions of Jawad and Watt (1986). There are clearly many orders or magnitude too few direct interactions of X-ray photons, or electrons, with the enzymes for these processes to be responsible for the mean of one inactivating event per enzyme which must occur at the D37 dose. Jawad and Watt (1986) concluded that the enzyme inactivation was predominantly due to direct interaction of an X-ray photon with a non-metal atom of the enzyme, but our analysis shows that this is not possible by five orders of magnitude. Of the possible mechanisms (a)-(d), the only one which remains feasible in this experimental system is the indirect action of radiolysis products from the solution (d). Diffusion distances of the order of 0.1 micron may be quite adequate for such inactivation. The situation would be very different for enzymes or other molecules within mammalian cells where diffusion distances are very much smaller (probably of the order of a few nanometres). Our analysis leaves unexplained the fairly small (20 per cent) change in effectiveness reported by Jawad and Watt (1986) for X-ray energy above, as compared to below, the K-absorption edge of Fe. The experimental observation is directly dependent on the accuracy of the dosimetry at these two energies; we have made no attempt to evaluate this.

Dihydroorotate Oxidase↗