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D T Goodhead

Publications and source records attributed to D T Goodhead.

At least 91 records · Page 5Linked to original sources
PubMed1987

The effect of 238Pu alpha-particles on the mouse fibroblast cell line C3H 10T1/2: characterization of source and RBE for cell survival.

Considerable interest has been aroused in recent years by reports that the transforming and carcinogenic effectiveness of low doses of high LET radiations can be increased by reducing the dose rate, especially for transformation of 10T1/2 cells in vitro by fission-spectrum neutrons. We report on conditions which have been established for irradiation of 10T1/2 cells with high LET monoenergetic alpha-particles (energy of 3.2 MeV, LET of 124 keV microns-1) from 238Pu. The alpha-particle irradiator allows convenient irradiation of multiple dishes of cells at selectable high or low dose rates and temperatures. The survival curves of irradiated cells showed that the mean lethal dose of alpha-particles was 0.6 Gy and corresponded to an RBE, at high dose rates, of 7.9 at 80 per cent survival and 4.6 at 5 per cent survival, relative to 60Co gamma-rays. The mean areas of the 10T1/2 nuclei, perpendicular to the incident alpha-particles, was measured as 201 microns2, from which it follows that, on average, only one in six of the alpha-particle traversals through a cell nucleus is lethal. Under the well-characterized conditions of these experiments the event frequency of alpha-particle traversals through cell nuclei is 9.8 Gy-1.

Alpha Particles↗
PubMed1987

Radiobiology of ultrasoft X rays. I. Cultured hamster cells (V79).

Ultrasoft X rays (approximately less than keV) provide a useful probe for the study of the physical parameters associated with the induction of biological lesions because the spatial scale of their energy depositions is of nanometer dimensions, comparable to that of critical structures within the cell. We report on cell-killing experiments using cultured hamster cells (V79) exposed to carbon K (0.28 keV), aluminum K (1.5 keV), copper K (8.0 keV), and 250 kVp X rays, under oxic and hypoxic conditions, and as a function of cell-cycle phase. Our principal results are: RBE increases with decreasing X-ray energy; OER decreases with decreasing X-ray energy; and cell-cycle response is similar for all X-ray energies. Our RBE results confirm earlier observations using ultrasoft X rays on mammalian cells. The shapes of fitted curves through the data for each energy are statistically indistinguishable from one another, implying that the enhanced effectiveness is purely dose modifying. The results reported herein generally support the view that single-track effects of radiation are predominantly due to very local energy depositions on the nanometer scale, which are principally responsible for observed radiobiological effects.

Animals↗
PubMed1986

The induction of chromosome exchange aberrations by carbon ultrasoft X-rays in V79 hamster cells.

V79 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 (approximately less than 7 nm) that they produce in the cell. This implies either that the participating DNA helices must be lying extremely close together at the time of radiation damage, so that one track can effectively damage both helices, or that only one radiation-damaged chromosome is needed to promote an exchange event.

Animals↗
PubMed1986

Effectiveness of 1.5 keV aluminium K and 0.3 keV carbon K characteristic X-rays at inducing DNA double-strand breaks in yeast cells.

Induction of DNA double-strand breaks in diploid wild-type yeast cells, and inactivation of diploid mutant cells (rad54-3) unable to repair DNA double-strand breaks, were studied with aluminium K (1.5 keV) and carbon K (0.278 keV) characteristic X-rays. The induction of DNA double-strand breaks was found to increase linearly with absorbed dose for both characteristic X-rays. Carbon K X-rays were more effective than aluminium K X-rays. Relative to 60Co gamma-rays the r.b.e.-values for the induction of DNA double-strand breaks were found to be 3.8 and 2.2 for carbon K and aluminium K X-rays respectively. The survival curves of the rad54-3 mutant cells were exponential for both ultrasoft X-rays. For inactivation of rad54-3 mutant cells, the r.b.e.-values relative to 60Co gamma-rays were 2.6 and 2.4 for carbon K and aluminium K X-rays, respectively. The DNA double-strand break data obtained with aluminium K and carbon K X-rays are in agreement with the data obtained for gene mutation, chromosome aberrations and inactivation of mammalian cells, suggesting that DNA double-strand breaks are the possible molecular lesions leading to these effects.

DNA↗
PubMed1985

Dosimetry comparison and characterisation of an Al K ultrasoft x-ray beam from an MRC cold-cathode source.

Ultrasoft x-rays of 0.3-5 keV have provided a unique tool for the investigation of intracellular mechanisms of radiation action in biological organisms, including mammalian cells. However, their use presents unique practical problems in dosimetry and experimental design. Detailed interpretation of the biological results requires reliable dosimetry and well characterised monoenergetic beams. This paper presents a comparison between two fundamentally different dosimetric techniques, namely the ionisation current in an extrapolation chamber and photon counts in a proportional counter. Agreement within 7% was obtained when these two methods were applied to an Al K x-ray beam (1.5 keV) from an MRC cold-cathode transmission target discharge tube as previously used in many biological experiments. Photographic film was calibrated as a relative dosimetric technique and used for investigation of the intensity uniformity of the radiation field. These techniques provide a comprehensive characterisation of the beam in the position of the biological cells, including photon flux (or absorbed dose rate), spectral purity (showing much less than 1% bremsstrahlung relative to characteristic Al x-rays) and uniformity over the irradiation area (within about 5% for mammalian cell irradiations).

Cell Survival↗
PubMed1985

Saturable repair models of radiation action in mammalian cells.

Most quantitative models of radiation action in mammalian cells make the implicit assumption that all relevant repair processes proceed in a dose-independent manner. Thus it is implicitly assumed that the repair processes (1) follow totally unsaturated kinetics, (2) are not themselves inactivated by the radiation, and (3) are not enhanced by the presence of radiation damage. Contradiction of any of these three assumptions could have important theoretical and practical implications. The possible relevance of (1) and (2) in mammalian cells is discussed by considering a selection of saturable repair (and related) models. Repair inactivation is improbable, but repair saturation provides a ready explanation of common radiobiological phenomena without the need for the existence of "sublethal" damage. Furthermore, such models can "explain" additional phenomena which appear as contradictions to some sublethal damage models. Recent experiments by Wheeler and Wierowski have demonstrated the existence of dose-dependent repair of DNA damage in mammalian cells.

Animals↗
PubMed1984

Proton-induced characteristic x-rays: a versatile source of ultrasoft x-rays for biological and biochemical investigations.

Very low energy ( ultrasoft ) x-rays of 0.3-5 keV have provided a unique tool for investigation of mechanisms of radiation action, especially with respect to the energy and spatial properties of critical radiation damage in mammalian cells. Experimental investigations to date have been partially limited by the availability and characteristics of suitable ultrasoft x-ray sources. The suitability of small electrostatic proton accelerators, such as exist in many laboratories, have been investigated as a means of producing a secondary beam of ultrasoft x-rays suitable for irradiation of biological and biochemical systems. Results are presented on the physical characteristic of carbon K (0.28 keV) and aluminium K (1.5 keV) ultrasoft x-ray beams produced by bombardment of solid targets of carbon and aluminium with protons of energies up to 750 kV and currents up to 500 microA. These characteristics are compared with those of a cold cathode discharge ultrasoft x-ray tube previously used for mammalian cell investigations. It is seen that the proton accelerator produces much more versatile beams of characteristic ultrasoft x-rays which greatly extend the scope for future experiments on mammalian cells, micro-organisms and biochemical systems. Nevertheless there are situations in which the cold-cathode discharge tube will remain the source of choice and there are other situations, requiring for example energies between characteristic lines, where the greatly more complex synchrotron radiation sources are required.

Animals↗
PubMed1983

Estimation of a single property of low LET radiations which correlates with biological effectiveness.

The biological effectiveness of ionising radiation is believed to be related to the initial structure of the radiation tracks. In this paper, an attempt is made to identify a single physical property of the radiation field that correlates with relative biological effectiveness. This property has been sought in terms of a minimum amount of energy deposition in a certain volume. In order to quantify this approach detailed Monte Carlo track structure simulations have been made of x-rays of widely differing energies and the results have been compared with previously reported experiments of cell killing by these radiations. In terms of the above threshold energy concept, we have thus identified a putative critical property of radiations of low ionisation density such as x-rays, namely the rare occurrence of energy deposition of greater than or equal to 100 eV in a volume of about 3 nm diameter.

Cell Survival↗
PubMed1982

The relative biological effectiveness of fast neutrons (42MeVd leads to Be) for early and late normal tissue injury in the pig.

Early and late radiation damage has been investigated in a number of normal tissues in the pig after irradiation with single doses of neutrons produced by 42MeV deuterons on beryllium. The results have been compared with data obtained after irradiation with single doses of 250kV X rays. In the skin a low RBE value of approximately 1.2 was obtained for the early (3-9 week) epithelial reaction. For the subsequent dermal vascular response, higher RBE values in the range of 1.35-1.6 were obtained: the RBE decreasing with an increase in the neutron dose. For late skin damage, assessed by the relative reduction in the linear dimensions of an irradiated field, a RBE value of approximately 1.5 was obtained. In the kidney the RBE value, for a neutron dose level (550 cGy) at which renal function was just preserved, was 2.0. A lower value of 1.7 was found for doses resulting in a loss of renal function. The results of 133Xenon clearance studies showed two waves of impaired ventilation function in the irradiated lung. In the acute reaction (3-9 months), at a dose level consistent with just preserving normal ventilation function, the RBE value was less than 1.2. For late lung damage (15-24 months) the RBE value was higher, 1.4. For the rectum, methods are presently only available for assessing acute damage. A RBE of 2.0 was found for neutron doses in the range 350-575 cGy. The RBE values for early endpoints in the skin, lung and gut of the pig are comparable with those published previously for other species, including man. The values for late effects in pig skin and lung were higher than for early damage in those tissues.

Animals↗
PubMed1981

Is selective absorption of ultrasoft x-rays biologically important in mammalian cells?

This paper tests whether photon absorption processes in particular atomic element(s) may be responsible for the observed high relative biological effectiveness (RBE) of ultrasoft X-rays. The effectiveness of titanium K characteristic X-rays (4.55 keV) is compared with previous observations for aluminium (1.5 keV) and carbon (0.28 keV) K ultrasoft X-rays. For a given absorbed dose, five times more Ti K than Al K photons are absorbed in phosphorus; since Al K X-rays are observed to be more effective in killing human and hamster cells it is concluded that absorption in phosphorus does not play a dominant lethal role. This is supported by the observation that the absolute number of Al K photons absorbed in phosphorus of DNA of human fibroblasts is less than 1 per lethal event. For no element is the relative number of absorbed photons of the three X-ray energies even approximately proportional to their observed RBEs. The effectiveness of ultrasoft X-rays is apparently not due to selective absorption but rather to the secondary electrons; consequently the mechanism of action should be common to the large numbers of low energy secondary electrons produced by most other ionising radiations, including gamma-rays.

Aluminum↗
PubMed1980

Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions. IV. Biophysical interpretation.

A biophysical analysis is made of the results of recent experiments which used accelerated heavy ions of 20 to 470 keV micron-1 to induce inactivation and mutation (resistance to 6-thioguanine) in cultured V79 Chinese hamster cells and HF19 human diploid fibroblasts. It is shown that the discrete nature of the primary ions must be explicity taken into account before the numbers of induced lethal and mutagenic lesions can be deduced from the observed radiosensitivities. The measured numbers of lesions produced by the radiations of different LET are compared with the relative numbers predicted by various models of radiation action. The observations can be explained on the hypothesis that each lethal lesion is produced by a deposition of small energy (small number of ionizations) in a distance of about 3 nm. Two different lesions appear to be involved, one of which requires greater than or equal to 100 eV and is dominant with low-LET radiations, and the other requires greater than or equal to 300 eV and is dominant at high-LET. Similar conclusions may apply to mutagenic lesions except that the mechanism which dominates at high-LET requires significantly more than 300 eV. More precise assessments of the hypothesis and these numerical values must await detailed track structure calculations of the radiation on the nanometre scale. Alternative models which invoke 'accumulation of sublethal damage' or 'interaction between sublesions', over distances of the order of microns, do not provide a consistent explanation of the observations. This suggests that the frequently observed curvature of low-LET dose-responses is not due to interaction between sublesions but rather to some other mechanism such as a dose-dependent repair process. It is also shown that low velocity, high-LET ions produce an average of appreciably less than one lethal lesion in traversing the nucleus of the above mammalian cells; 90 keV micron-1 helium ions produce about 0.03-0.06 lethal lesions micron-1 of track through the nucleus of the cells of thickness about 7 microns. Some estimates are also made of the size of the nuclear region which is sensitive to the induction of mutation to 6-thioguanine-resistance; it is concluded that this region extends beyond the DNA of the structural gene itself.

Animals↗
PubMed1980

Chromosome aberrations induced in human lymphocytes by ultrasoft Al (K) and C (K) X-rays.

Induction of structural chromosome aberrations was studied in human peripheral blood lymphocytes irradiated in the unstimulated state with ultrasoft X-rays. Aluminium K X-rays (1.49 ke V) and carbon K X-rays (0.28 ke V) were used. The frequencies of dicentric aberrations and of excess acentric fragments were found to increase approximately linearly with absorbed dose of both radiations. Carbon X-rays were more effective than aluminium X-rays. The corresponding linear yield coefficients for dicentrics are (3.7 X 10(-1)) Gy-1 and (2.2 X 10(-1)) Gy-1 respectively. AT low doses both these radiations are more effective than hard X-rays in producing dicentric aberrations, but at high doses aluminium X-rays are less effective than hard X-rays because of the large positive curvature of the hard X-ray dose-response. The most significant observation of these experiments is that electrons of less than 280 eV, produced by carbon X-rays, are efficient in producing dicentric aberrations. This implies that single local energy events of about 14 ionizations with in less than 7 nm are able to produce exchange aberrations.

Cell Division↗
PubMed1979

Effectiveness of 0.3 keV carbon ultrasoft X-rays for the inactivation and mutation of cultured mammalian cells.

Carbon K characteristic ultrasoft X-rays of energy 0.278 keV were found to be effective in inducing inactivation and mutation to thioguanine resistance in cultured V79 Chinese hamster cells and human diploid fibroblasts. These X-rays act as a probe of the sensitive sites within the cells since they produce low-energy photoelectron tracks of range about 7 nm; this is an order of magnitude smaller than those produced by the 1.5 keV aluminium X-rays used in previous studies. A detailed interpretation of the results requires assumptions to be made about the positions of the sensitive sites within the cells but, for any reasonable set of assumptions, the carbon X-rays are found to be more effective than gamma-rays and are probably at least as effective as long tracks of helium ions of similar LET. These observations extend the conclusions previously drawn from the observed effectiveness of aluminium X-rays regarding the sizes of the subcellular sites involved in inactivation and mutation. They imply that the sensitive sites smaller than about 7 nm, and that highly localized energy depositions consisting of less than or approximately 14 ionizations are sufficient to produce biological effects. These results are also in contradiction to models of radiation action which require relatively large sites, such as the usual form of the 'theory of dual radiation action'.

Aluminum↗
PubMed1979

Mutation and inactivation of cultured mammalian cells exposed to beams of accelerated heavy ions. I. Irradiation facilities and methods.

This paper, which is the first of four covering the inactivation of clonogenic capacity and induction of mutation in cultured mammalian cells, deals briefly with the general aims of the work and describes the irradiation techniques used. Human diploid fibroblasts and V79 Chinese hamster cells were irradiated as monolayers with ions of helium, boron or nitrogen at LET's in the range 20 to 479 keV micrometer-1 in H2O. The physical aspects of the irradiation including measurement of ion energies, dosimetry and uniformity of dose and also the methods of handling large numbers of samples are described in detail. Subsequent papers will present the biological methods and results and a biophysical analysis of the data.

Animals↗