Search PubMed⌕ Search

Biomedical subjects

A A Edwards

Publications and source records attributed to A A Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1997

The use of chromosomal aberrations in human lymphocytes for biological dosimetry.

The scoring of chromosomal aberrations in human lymphocytes provides the most sensitive method known for biological dosimetry. By scoring dicentrics in the full genome of 500 cells, average whole-body doses of about 0.1 Gy of X or gamma rays may be detected and higher doses estimated. Acute doses above about 0.2 Gy can be estimated more accurately than similar chronic doses. For radiations of higher LET, for example those encountered in the space environment, the limits of detection in grays are lower. However, expressed in sieverts, the limits of detection are more nearly independent of radiation quality. This suggests for exposure to space radiations that it may be possible to convert the yield of aberrations directly to an average whole-body dose in sieverts, which can be used as an estimate of effective dose. The scoring of translocations involving about 20% of the genome in 1000 cells using fluorescence in situ hybridization painting techniques results in a reduced sensitivity at low doses so that acute X-ray doses of about 0.3 Gy and chronic doses of about 0.4 Gy are at the limit of measurement. Better sensitivity can be achieved by scoring more cells or by using more chromosomes in color combinations, but a final limit to these approaches exists because of the higher level of spontaneous translocations than dicentrics in cells of unirradiated persons.

Aerospace Medicine↗
PubMed1996

On the mechanism of the formation of chromosomal aberrations by ionising radiation.

The results of applying a biophysical model to describe the production of chromosomal aberrations in human lymphocytes are presented. The model describes energy deposition in cell nuclei, the conversion to DNA double-strand breaks, and the repair and misrepair of those breaks to form aberrations. The repair and misrepair of double-strand breaks are expressed as a competition process based on the concept that the probability of exchange depends upon the spatial separation of the breaks. Results are restricted to photon irradiations. We show that the model leads to the familiar linear-quadratic equation for the dependence of exchange aberration yield on dose. Exchanges between two DNA breaks along the same track determine the linear term, and exchanges between those in different tracks determine the quadratic term. We demonstrate the importance of electron track structure in the prediction of the linear term and show that the low-dose RBE between x- and gamma-rays depends not only on the physical description of the track but also the biological repair function. For intratrack exchanges, we show that the double-strand breaks are very close, on average about 30 nm apart. For intertrack exchanges, the mean separation of breaks is calculated to be about 2 mu m. There is a clear separation of the two modes of action. In addition, the increased effectiveness of the track ends of electrons is shown.

Cell Nucleus↗
PubMed1996

Modelling the kinetics of chromosome exchange formation in human cells exposed to ionising radiation.

A biophysical model has been applied to study the kinetics of chromosome exchange formation in human cells. Chromosomal exchange induction (for example dicentrics) by ionising radiation was modelled by means of the Monte Carlo technique. This involved energy deposition by electrons, production of chromosomal breaks (assumed to be DNA double-strand breaks) and their repair and exchange. Exchanges were assumed to result from pairwise interaction between two DNA breaks in a distance-dependent manner. The rate at which exchanges are formed was found to depend upon how the exchange to no-exchange probability ratio varied with time. The assumption that this ratio did not alter with time produced a time constant for the formation of exchanges which was exactly half that of the repair time constant. Longer time constants could not be accommodated unless the probability ratio for exchange increases with time. Different time constants for inter- and intratrack exchanges could be achieved on the basis of DNA double-strand break separation.

Animals↗
PubMed1995

X-ray biological dosimetry performed by selective painting of human chromosomes 1 and 2.

Fluorescence in situ hybridization with a cocktail of whole-chromosome probes, specific for human chromosomes 1 and 2, was performed to analyze the induction of translocations and dicentrics in human peripheral blood lymphocytes exposed to 100 KVp X-rays and cultured for 48 h. The dose-response curves for both aberration types were linear-quadratic, with similar coefficients, and after correction for genome content were a little lower than the dose-response curve for dicentrics established by conventional analysis. Three doses were also assessed after 76-h culture. The dicentric yield at 76 h was reduced compared with that at 48 h because of the existence of second and third division metaphases. The translocation yield did not reduce except at 4 Gy. The frequency of cells containing both dicentrics and translocations suggested that their occurrence is not correlated. The importance of stating the scoring criteria and of specifying the different types of aberrations is stressed.

Cells, Cultured↗
PubMed1995

Fluorescence in situ hybridization detection of chromosomal aberrations in human lymphocytes: applicability to biological dosimetry.

Human lymphocytes in G0 have been irradiated with X-ray doses from 0 to 4.0 Gy. Metaphase chromosomes 2, 3 and 5 and all centromeres were painted using fluorescence in situ hybridization (FISH) probe libraries. Dicentrics, centric rings and acentrics in the whole genome as well as translocations involving the painted chromosomes were recorded. The translocations were subdivided as complete or incomplete. Interstitial insertions and inversions were also noted. The observations were also recorded according to the Protocol for Aberration Identification and Nomenclature Terminology (PAINT) system of scoring. Given that the painted chromosomes comprise 20.4% of the genome it was found that the yield of bicoloured dicentrics was consistent with the yield of dicentrics in the whole genome. The yield of radiation-induced translocations was not significantly higher than that of bicoloured dicentrics. Of the translocations, 60% were complete and it was concluded that the majority of dicentrics and translocations are complete exchanges. Chromosome 5 took part in exchanges marginally more commonly than its length suggests, but it is not known if this is a property of the chromosome or whether it is a donor-dependent observation. The PAINT system of recording rearrangements was examined and the suggested numerical interpretation of this nomenclature was considered to be unsuitable for use in the estimation of dose for cases of accidental overexposure.

Adult↗
PubMed1994

Modelling of DNA breaks and the formation of chromosome aberrations.

We present results of some calculations that convert double-strand breaks to dicentrics by means of a repair-misrepair model. The method uses Monte Carlo techniques to determine the positions of the double-strand breaks and to determine the dicentric yields for comparison with those obtained experimentally in human lymphocytes following irradiation in G0. The model is able to describe the linear-quadratic curves of dicentric yield following low LET irradiation, but underpredicts by a factor of about 1.5-2.0 the high LET neutron curves. The effects of including corrections for interphase death are demonstrated. The reasons for the discrepancy at high LET are discussed and suggestions for an improvement to the fit are made.

Chromosome Aberrations↗
PubMed1994

Death of a classified worker probably caused by overexposure to gamma radiation.

This paper describes the case of an industrial radiographer who was seriously overexposed to gamma radiation. The exact circumstances of this exposure were not established but it was concluded that he was repeatedly irradiated probably to a total average whole body dose of at least 10 Gy over several years. Also, a much larger dose to a hand required its partial amputation. He developed myelodysplasia, which progressed to acute myeloid leukaemia from which he died. Karyotypic examination of the leukaemic blasts showed changes very similar to those associated with secondary leukaemia that may develop after radio or chemotherapy. The paper describes his medical case history, the investigation of his workplace, and the attempts to estimate his radiation dose by chromosomal analysis of blood lymphocytes and electron spin resonance of dental enamel and bone.

Acute Disease↗
PubMed1993

Reflex sympathetic dystrophy syndrome.

Reflex sympathetic dystrophy syndrome is a troublesome, complex disorder that presents with chronic, unexplained aching or burning pain, the intensity of which is incommensurable with the original injury. Six diagnostic criteria have been described by Genant et al: pain and tenderness in the extremities; swelling of soft tissue; diminished motor function; trophic skin changes; vasomotor instability; and patchy osteoporosis. Currently, the most widely accepted etiology is an initial vasomotor reflex spasm occurring after an injury to the extremity, followed by a loss of vascular tone, persistent vasodilation, and rapid bone resorption.

Adult↗
PubMed1993

[Chromosomal damages in human lymphocytes induced by low doses of irradiation].

The observation of chromosomal aberrations in circulating lymphocytes is the most sensitive biological indicator of human exposure to ionising radiation. Data at low doses from in vivo and in vitro irradiated lymphocytes are reviewed. Statistical uncertainties mean that no resolution can be made between a linear or threshold response in the range 0-20 mGy of low LET radiation. Above 20 mGy the data conform to the linear quadratic model. The possibility of measuring chromosomal aberrations for dose estimation, to be used in conjunction with epidemiological studies on groups of persons exposed to radiation from the Chernobyl accident, is discussed.

Cells, Cultured↗
PubMed1992

A survey of lymphocyte chromosomal damage in Slovenian workers exposed to occupational clastogens.

Assays for sister-chromatid exchanges (SCE), unstable chromosome and chromatid aberrations and micronuclei were performed on blood lymphocytes from persons exposed protractedly to radiation or chemical hazards in the workplace. There was a general tendency with all endpoints examined for the yields to increase with years of working in the industry. This was especially marked for SCE. By comparison with a control group of administrative workers the levels of damage were higher, usually significantly so, in the occupational groups. These comprised workers at a nuclear research reactor, a hospital diagnostic X-ray department, a coal mine and a mercury ore mine.

Adult↗
PubMed1992

Chromosomal data relevant for Q values.

It has been known for many years that relationships between absorbed dose and biological effect vary with the type of radiation. In particular, neutrons and alpha particles are more damaging than x or gamma radiations. This applies to a range of biological effects such as cell killing, chromosome aberrations, cell mutation, cell transformation as well as life shortening and cancer induction in animals. The application of this knowledge to devise a scheme for specifying the quality factor (Q) in radiological protection has been the subject of much debate. There are no tumour data in humans from which the quality factor may be derived. The problems of using animal and cell transformation data which are probably the next best choice are discussed. The extensive data base on chromosomal aberrations in human lymphocytes is described and discussed in terms of relevance to deducing quality factors. Particular emphasis is placed on data obtained at low doses and low dose rates.

Animals↗
PubMed1992

Chromosomal aberrations in human lymphocytes induced in vitro by very low doses of X-rays.

This paper presents results of a collaborative experiment between six laboratories which examined the yields of unstable chromosomal aberrations in human lymphocytes induced in vitro by X-rays over the dose range 0-300 mGy. The work included data points of nominal doses of 0, 3, 5, 6, 10, 20, 30, 50 and 300 mGy. Cells from 24 donors were examined and a total of about 300,000 metaphases were scored. The work was undertaken to determine the limits of sensitivity of the system taking into account variations in scoring data due to inter-donor sample and inter-laboratory effects. Despite the existence of these effects, aberration yields significantly in excess of control values were seen at doses greater than 20 mGy and these were consistent with a linear extrapolation from higher doses. Below 20 mGy the observed dicentric yields were generally lower than background, but not significantly so. Excess acentric aberrations, on the other hand, and centric rings, were higher than the controls but the increase was usually not significant. It is concluded that the statistical uncertainties are such that below 20 mGy this technique cannot distinguish between a linear or a threshold model.

Chromosome Aberrations↗
PubMed1990

The relationship between colony-forming ability and chromosomal aberrations induced in human T-lymphocytes after gamma-irradiation.

Using aliquots from the same samples of irradiated normal human blood, T-lymphocyte survival was measured by (a) 14-day colony growth, (b) the proportion of chromosomally normal first post-irradiation metaphases and (c) the proportion of cells not suffering interphase death and delay within 48 h after irradiation. Combining (b) and (c) gives a prediction of the proportion of cytogenetically undamaged cells which reach metaphase after 48 h. These cells should be capable of producing viable colonies under suitable culture conditions. A comparison of these values with those observed in (a) shows a reasonable agreement in accordance with the hypothesis that gross chromosomal damage and cell reproductive death are closely related.

Cell Survival↗
PubMed1990

Chromosomal radiosensitivity of lymphocytes from Alzheimer's disease patients.

We have examined chromosome aberrations in gamma irradiated (3 Gy) lymphocytes from five patients with Alzheimer's disease (AD). In each case, the number of dicentrics was significantly higher than the number in irradiated lymphocytes from five age matched normal subjects, the mean value for AD cells being about 25% higher. There was no significant difference in number of acentrics between AD and normal cells. Examination of the number of first, second, and third division metaphases, using fluorescence plus Giemsa staining, indicated that there was no difference in cycling time between AD and normal cells, and that after irradiation both groups showed the same mitotic delay. The similarity of our findings to those of others with irradiated Down's syndrome cells (from adult patients) is discussed.

Aged↗
PubMed1989

Sister-chromatid exchanges induced by mitomycin C after acute or chronic exposure of human lymphocytes to a low dose of X-rays.

Human peripheral blood lymphocytes from 10 male donors were exposed to mitomycin C with and without prior irradiation with 0.01 Gy X-rays. Acute or chronic irradiation of lymphocytes in G1 resulted in a decrease in the subsequent level of mitomycin C-induced sister-chromatid exchange aberrations. The effect was small (approximately 10%) with evidence of some variability between donors. By contrast no adaptive response was observed if the cells were treated in G0.

Adaptation, Physiological↗