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A A Edwards

Publications and source records attributed to A A Edwards.

At least 19 recordsLinked to original sources
PubMed2006

What are the risks from medical X-rays and other low dose radiation?

The magnitude of the risks from low doses of radiation is one of the central questions in radiological protection. It is particularly relevant when discussing the justification and optimization of diagnostic medical exposures. Medical X-rays can undoubtedly confer substantial benefits in the healthcare of patients, but not without exposing them to effective doses ranging from a few microsieverts to a few tens of millisieverts. Do we have any evidence that these levels of exposure result in significant health risks to patients? The current consensus held by national and international radiological protection organizations is that, for these comparatively low doses, the most appropriate risk model is one in which the risk of radiation-induced cancer and hereditary disease is assumed to increase linearly with increasing radiation dose, with no threshold (the so-called linear no threshold (LNT) model). However, the LNT hypothesis has been challenged both by those who believe that low doses of radiation are more damaging than the hypothesis predicts and by those who believe that they are less harmful, and possibly even beneficial (often referred to as hormesis). This article reviews the evidence for and against both the LNT hypothesis and hormesis, and explains why the general scientific consensus is currently in favour of the LNT model as the most appropriate dose-response relationship for radiation protection purposes at low doses. Finally, the impact of the LNT model on the assessment of the risks from medical X-rays and how this affects the justification and optimization of such exposures is discussed.

Dose-Response Relationship, Radiation↗
PubMed2005

Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay.

The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

Acute Disease↗
PubMed2005

6-alkylsalicylic acids and 6-alkylresorcylic acids from ants in the genus Crematogaster from Brunei.

The defensive chemistry of two species of ants from Brunei in the genus Crematogaster (Physocrema group) has been investigated. Ants in this group release a white secretion from hypertrophied metapleural glands on their thorax when they are disturbed. Previously, one species in this group has been shown to produce alkylphenols and alkylresorcinols. In the present investigation, similar compounds along with salicylic acids and resorcylic acids that are anacardic acid and olivetolic acid homologs, respectively, are described from two species. The structures of these compounds were suggested by their spectroscopic data and confirmed by direct comparison with synthetic samples. Some of these compounds occur in lichens and have well documented physiological activities.

Anacardic Acids↗
PubMed2005

Translocation yields in peripheral blood lymphocytes from control populations.

PURPOSE: To record the latest information on control levels of translocations in cultured human lymphocytes. MATERIALS AND METHODS: Control-level data from seven European laboratories that are using fluorescence in situ hybridization (FISH) techniques for retrospective biological dosimetry have been combined in a meta-analysis. After correction for the differing probe combinations used, tests of consistency are performed. The combined data have been used to test for individual variation, systematic variation with age, gender and smoking habits. RESULTS: There is a strong variation of translocation yield with age but no variation was detectable with gender or smoking habits. After correction for age, homogeneity tests showed that about 10% of individuals were outside the 95% confidence limits as opposed to 5% expected. From a total of 385, there is an excess of about 20 individuals most of whom have an unexpectedly high yield of translocations. CONCLUSIONS: For retrospective biological dosimetry purposes a generic age-dependent control level can be assumed. No other lifestyle factors such as smoking appear to have a significant effect on translocation yield.

Adolescent↗
PubMed2005

The yield of radiation-induced chromosomal aberrations in first division human lymphocytes depends on the culture time.

PURPOSE: To investigate two long-held beliefs in radiation cytogenetics that were seemingly contradicted by reports that: (a) protracting gamma-ray exposures over 0.5 h halves the induced aberration yield compared with acute exposure, and (b) that induced aberration yields in guaranteed first in vitro division metaphases (M1) vary with culture time. MATERIALS AND METHODS: Replicate blood samples were exposed for 3 min to 3.0 Gy gamma-rays and standard phytohaemagglutinin stimulated lymphocyte cultures were harvested at 10 times ranging from 45-72 h. Forty-eight hour cultures were also made from blood exposed to 3.0 Gy for 30 min. Slides were differentially stained, combining the harlequin method with fluorescent in-situ hybridization (FISH) painting of chromosomes 2, 3 and 5. M1 metaphases were scored for 1- and 2-way translocations involving the painted chromosomes and all unstable aberrations in the full genomes. RESULTS: Dicentric and translocation yields from the 30 min exposure were approximately 10% lower than in 48 h cultures from cells exposed for 3 min, although this reduction is not significant. Dicentric aberration yields from the 3 min exposed cells cultured over the range 45-72 h remained constant up to 51 h then rose to a different constant value beyond 60 h. The increase at 60-70 h compared with the yield at 48 h was about 50%. A marginal increase at later times was also observed for translocations. CONCLUSION: The protracted exposure experiment produced results consistent with the G-function hypothesis that models the dose rate effect. Therefore the previous report of a marked departure from this model was not confirmed. The reports of aberration yields increasing with time of arrival at metaphase were confirmed. Possible explanations are discussed; the intercellular distributions of aberrations, or of doses to the cells or heterogeneous radiosensitivity of lymphocyte sub-populations. None alone seems sufficient quantitatively to explain the magnitude of the effect. The implications for biological dosimetry, which employs cultures times of approximately 48 h, are considered to be minor.

Adult↗
PubMed2005

Review of translocations detected by FISH for retrospective biological dosimetry applications.

Several European laboratories have combined their research efforts to arrive at a consensus view on using fluorescence in situ hybridisation (FISH) for retrospective dosimetry. The aim of this review is to report these views and to highlight some areas where further work is needed. Translocations in the stable cells should be measured only in the cells that contain the full complement of the painted material. Two-way and one-way translocations should be combined with equal weight. The control level of translocations has a strong dependence on age, which has now been measured and the system has been calibrated. In conclusion, the technique works and a lifetime dose to the bone marrow from low-linear energy transfer radiation of 0.5 Gy above normal background levels can be measured for any individual. The main application is considered to provide an independent verification of lifetime doses to individuals who might form a part of an epidemiological study.

Calibration↗
PubMed2004

A cytogenetic follow-up of some highly irradiated victims of the Chernobyl accident.

A follow-up of 10 highly irradiated men, mostly reactor crew, from the Chernobyl accident is described. Their pre-accident medical conditions and relevant medical status approximately 10-13 y later are listed. A comparison is made between estimates of their average whole-body penetrating radiation doses derived from several biological parameters. First estimates were based on their presenting severity of prodromal sickness, early changes in blood cell counts and dicentric chromosome aberrations in lymphocytes. In three cases ESR measurements on tooth enamel were also made. Retrospective dosimetry using FISH translocations was attempted 10-13 y later. This showed good agreement for those patients with the lower earlier dose estimates, up to about 3 Gy. For the others, extending up to about 12 Gy, the translocations indicated lower values, suggesting that in these cases translocations had somewhat declined. Repeated chromosomal examinations during the follow-up period showed an expected decline in dicentric frequencies. The pattern of decline was bi-phasic with a more rapid first phase, with a half-life of approximately 4 months followed by a slower decline with half-lives around 2-4 y. The rapid phase persisted for a longer time in those patients who had received the highest doses. 10-13 y later dicentric levels were still above normal background, but well below the translocation frequencies.

Adult↗
PubMed2004

The chemistry of exploding ants, Camponotus spp. (cylindricus complex).

A detailed comparative analysis of the exocrine chemistry of nine Bruneian Camponotus species in the cylindricus complex is reported. Workers of these species are known to have hypertrophied mandibular glands and release their glandular contents suicidally from the head by rupturing the intersegmental membrane of the gaster. All of the species produce mixtures of polyacetate-derived aromatics, including hydroxyacetophenones, which display pH-dependent color changes, and aliphatic hydrocarbons and alcohols. In addition, three species contained (6R)-2,6-dimethyl-(2E)-octen-1,8-dioic acid (9) or (3S)-8-hydroxycitro-nellic acid (10a), previously unreported from insects. These compounds were characterized from their spectral data, and confirmed by comparison with synthetic samples. The allomonal role of these compounds is based on numerous field observations, and their chemotaxonomic value is presented.

Acetates↗
PubMed2004

Chromosome aberrations induced in human lymphocytes by heavy charged particles in track segment mode.

Human blood was irradiated with accelerated ions: 20 MeV 4He, 425 MeV 12C and 1480 MeV and 996 MeV 16O. For each ion, the blood was exposed to a range of doses as thin specimens in the track segment mode, so that irradiations took place at nearly constant LETs of 31.4, 61, 52 and 69 keV microm(-1), respectively. Lymphocytes were cultured to the first in vitro metaphase, analysed for chromosomal damage and the dicentric aberration frequencies fitted to the linear quadratic model of dose-response. For these high LET radiations, the linear (alpha) yield coefficient predominated and increased with LET, at least up to 60 keV microm(-1). Apart from the 996 MeV oxygen ions, the data indicated the presence of a quadratic (beta) coefficient, statistically consistent with values obtained with low LET radiations. However, the associated uncertainties on the measured beta values were large, illustrating the general problem that beta is more difficult to measure against a dominating and ever-increasing alpha term. The existence or otherwise of a beta component of the dose-response at these radiation qualities has important consequences for modelling mechanisms of aberration induction by radiation.

Chromosome Aberrations↗
PubMed2004

Criticality accident dosimetry by chromosomal analysis.

The technique of measuring the frequency of dicentric chromosomal aberrations in blood lymphocytes was used to estimate doses in a simulated criticality accident. The simulation consisted of three exposures; approximately 5 Gy with a bare source and 1 and 2 Gy with a lead-shielded source. Three laboratories made separate estimates of the doses. These were made by the iterative method of apportioning the observed dicentric frequencies between the gamma and neutron components, taking account of a given gamma/neutron dose ratio, and referring the separated dicentric frequencies to dose-response calibration curves. An alternative method, based on Bayesian ideas, was employed. This was developed for interpreting dicentric frequencies in situations where the gamma/neutron ratio is uncertain. Both methods gave very similar results. One laboratory produced dose estimates close to the eventual exercise reference doses and the other laboratories estimated slightly higher values. The main reason for the higher values was the calibration relationships for fission neutrons.

Chromosome Aberrations↗
PubMed2003

Induction of chromosome aberration in human lymphocytes and its dependence on X ray energy.

The variations of dose response with X ray energy observed with the human lymphocyte dicentric assay is examined. In order to determine reliably the initial slopes (RBEm) many cells need to be analysed at low doses. Insufficient analysis may explain some reported interlaboratory differences in fitted dose-response coefficients. One such discrepancy at 150 kVp, E = 70 keV is examined. Data are also presented for an X ray spectrum of 80 kVp, E = 58 keV. Over the photon energy range 20 keV X rays to 1.25 MeV gamma rays RBEm varies by about a factor of 5, with the lower energies being more effective. This is consistent with microdosimetric theory. By contrast, in radiological protection a radiation weighting factor of 1.0 is assumed for all photons when assessing the risk of inducing cancer at low doses. The measured variations of biological effect with photon energy have led to suggestions that the lower energies, as used for some diagnostic radiology, carry a greater risk per unit dose than is normally assumed by those involved in radiological protection. Interpretation of the data reported in this paper does not support this view.

Cells, Cultured↗
PubMed2003

The present ICRP protection quantitites are seriously flawed. Opposing the proposition.

Our debaters have agreed to defend positions that appear to be diametrically opposed; nevertheless, they have acknowledged some common ground. Although it was not explicitly stated, they would no doubt agree that workers and the public are adequately protected by our present system of radiation regulations. Our debaters have overtly agreed that it would be desirable to have measurable radiation protection quantities. Whether or not this is advantageous, or even possible, will depend upon which argument swayed your opinion. The ICRP is presently examining its recommendations and will, over the next few years, update those recommendations. Therefore, the contributions of our debaters will surely be relevant to this process.

Humans↗
PubMed2002

Modelling radiation-induced chromosome aberrations.

PURPOSE: To review the data and models on the induction of chromosomal aberrations by a single acute dose of radiation, then critically to assess progress that has been made so far to make a judgement about prospects for increased understanding. MATERIALS AND METHODS: Drawing upon many years of personal experience, a consistent set of data on the radiation-induced dicentric yield in human lymphocytes was produced. Other data concerning the production of complex rearrangements and the time-course of the appearance of dicentrics has also been reviewed. Three basic models have been reviewed and compared with respect to their ability to predict the judged dose-effect relationships as well as the time-course and complexity of the aberration production. CONCLUSIONS: None of the three basic models alone can explain adequately all of the available data. A combination of the models has succeeded to a greater extent, but there is still no complete agreement. The major reason for the discrepancy between the measured yield curves and their predictions lies in the variation of the quadratic term in the dose-response relationship with increasing linear energy transfer. Further experimental work is required to resolve this.

Animals↗
PubMed2002

Cytogenic investigations of serious overexposures to an industrial gamma radiography source.

This paper describes the sequence of events, medical aspects and dose estimations for two radiographers and their driver who were seriously exposed to an iridium-192 industrial radiography source that became detached from its wind-out cable. The men came to medical attention about 1 month later by which time all three were severely leucopenic and one had skin burns on both hands. Doses were estimated by (i) physics calculations combined with their accounts of the event. (ii) the levels of depression of their blood neutrophils, (iii) electron spin resonance on tooth enamel and (iv) blood lymphocyte chromosomal analyses by the conventional dicentric and the fluorescence in situ hybridisation methods. Intercomparison of these methods for estimating doses showed a good level of agreement. In brief, the averaged whole body dose for the most seriously exposed man was about 2.5-3.0 Gy and for the others it was 1.0-2.0 Gy.

Acute Disease↗
PubMed2001

In vitro transmission of chromosomal aberrations through mitosis in human lymphocytes.

Stable and unstable chromosome aberrations in human lymphocytes exposed to 2 and 4Gy of X-rays in G(0) were analyzed in M1 and M2 cells harvested at 72h to investigate how the scoring protocol influences the yields of aberrations transmitted through one mitosis. Metaphase chromosomes 2, 3, and 5 were painted using fluorescence in situ hybridization (FISH) whole chromosome probes, together with a pan-centromeric probe and stained by the harlequin-FISH method, to allow the cell cycle status of each cell to be determined as it was scored. A strict scoring criterion was adopted so that each metaphase had to contain 46 centromeres and each dicentric/centric ring had to have an acentric present. In addition to scoring the painted material, unstable aberrations in the whole genome were also recorded. The yield of complete dicentrics decreased by more than a factor of 2 in going from M1 to M2. The decrease was greater at the lower dose. Two-way translocations appeared stable, but one-way translocations decreased. This suggests that if translocation yields are to be used for biological dosimetry purposes, then the two-way type should be used.

Adult↗