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Biomedical subjects

A A Edwards

Publications and source records attributed to A A Edwards.

At least 37 records · Page 2Linked to original sources

Lack of detectable transmissible chromosomal instability after in vivo or in vitro exposure of mouse bone marrow cells to 224Ra alpha particles.

Several studies over recent years have highlighted the possibility that radiation can induce transmissible genomic instability. Most of these involve in vitro irradiation and usually in vitro culture. Here it is reported that the short-half-life bone-seeking alpha-particle emitter (224)Ra did not induce excess transmissible chromosomal instability in CBA/H mouse bone marrow cells in a 100-day period after in vivo or in vitro exposure. Similarly, no excess transmissible chromosomal instability could be detected after in vivo whole-body X irradiation. It was noted, however, that short-term culture of murine bone marrow cells elevated yields of aberrations, as did transplantation of untreated marrow into radiation-ablated hosts. These findings emphasize the sensitivity of murine hemopoietic tissue to experimental manipulation and reinforce the importance of appropriate concurrent control experiments in any investigation of transmissible genomic instability.

Alpha Particles↗

A study to verify a reported excess of chromosomal aberrations in blood lymphocytes of Namibian uranium miners.

This report describes a study to verify an earlier report of excess chromosomal damage in the blood lymphocytes of uranium miners. Coded blood samples from 10 miners and 10 controls were analyzed conventionally for unstable aberrations and by FISH for translocations. Conventional analysis, scoring 1000 metaphases per subject, showed no significant difference between miners and controls in the frequencies of chromosome- and chromatid-type aberrations. Investigators at two laboratories undertook FISH analyses, each scoring 4000 metaphases per subject. When the data from each laboratory were examined separately, one found slightly more translocations in the miners while the other found fewer. In neither case was the difference significant at the 95% level of confidence. Combining the data likewise showed no significant excess of damage in the miners. This applied to simple one- and two-way translocations and to cells with complex exchanges. There was no correlation between levels of translocations and total lifetime doses from occupational and/or background irradiation. A borderline significant excess of rogue cells was found in the miners. This may be a chance observation, as these rare, highly abnormal cells are considered to be unrelated to radiation exposure and are probably due to a virus. The overall conclusion is that the frequency of chromosomal damage in the miners did not exceed that in the controls. Therefore, the result of the earlier study was not confirmed.

Chromosome Aberrations↗

Lymphocyte chromosomal aberrations and their complexity induced in vitro by plutonium-239 alpha-particles and detected by FISH.

G0 human lymphocytes were exposed in vitro to plutonium-239 alpha-particles, with doses ranging from 0 to 1.62 Gy, to provide a dose response curve and to compare complex rearrangements produced by high LET radiation with low LET data from previous work. Metaphase chromosomes 1 and 2 were painted using fluorescence in situ hybridization (FISH) whole chromosome probes. All unstable and stable aberrations involving the painted chromosomes were scored. The whole genome corrected alpha-coefficient for dicentrics was 0.244 +/- 0.023 and for total translocations 0.346 +/- 0.032, when considering simple and complex exchanges. The ratio of bicoloured total translocations to bicoloured dicentrics was 1.21 +/- 0.15 and the ratio of 2-way to 1-way translocations was 1.73 +/- 0.27 for apparently simple exchanges only. A correlation was noted between the distributions of dicentrics and translocations and this applied even when the complex rearrangements were removed. 20% of the observed rearrangements were complex and this observation was independent of dose. Qualitatively, following irradiation with alpha-particles the complex rearrangements observed were of a greater complexity than seen after X- or gamma-rays. Using the Savage and Simpson system to classify the complex rearrangements, the higher order complexes were found to be the most common type observed. However the insertion type increased while the 2F + 2G types decreased when complex rearrangements induced by alpha-particles were compared to those formed after X- or gamma-irradiation.

Alpha Particles↗

RBE of radiations in space and the implications for space travel.

Space travellers are irradiated with cosmic rays to a dose rate considerably higher than that received on earth. In order to make sensible judgements about space exploration, the risks to health of such radiation need to be assessed. Part of the assessment of risk is to allow for the enhanced biological effectiveness of high LET radiations with respect to others. In space the high LET radiations of concern are high energy neutrons and charged particles. At the doses and dose rates encountered in space, the important risk is the induction of cancer in the astronauts. For this biological end-point there is no direct human evidence for the relative effectiveness of these radiations. There are some data for neutrons for cancer and life-shortening in laboratory animals but these are for fission spectra neutrons, which are of lower energy than those encountered in space. There is a small amount of data for protons and high energy heavier charged particles. The remaining evidence comes from cellular experiments observing chromosome aberrations and gene mutations. From this sparse information, pragmatic choices need to be made for application to protection in space. The data are reviewed and the bases for the pragmatic choices discussed.

Animals↗

The role of cytogenetics in early triage of radiation casualties.

Preliminary dose estimates by chromosomal analysis can be made rapidly in order to supplement early triage of radiation casualties based on clinical signs. An in vitro simulation of an accident with many casualties receiving whole or partial body exposure in the range 0-8 Gy is described. Faced with an urgent need for rapid results, confirmation of clinical triage can generally be obtained from scoring 20 metaphases per subject. Scoring should be increased to 50 cells where there is disagreement with the initial assessments or evidence of significantly inhomogeneous exposure.

Chromosome Aberrations↗

Comparison of cytogenetic damage in cultured cells from cobalt-60 gamma-radiation and the Auger emitter zinc-65.

PURPOSE: To assess the ability of the Auger-emitting nuclide, zinc-65 (65Zn), relative to gamma-irradiation, to cause chromosomal aberrations in cultured rat prostate cells. MATERIALS AND METHODS: Rat prostate adenocarcinoma cells in culture were exposed to doses of 1, 2, 3 or 5 Gy of external gamma-irradiation for 24h or incubated with 0.7, 1.5, 1.8 or 2.8 MBq of 65Zn for 24 h. The uptake by and clearance from cells of 65Zn was measured. Metaphase spreads prepared from washed cells were scored for chromatid- and chromosome-type aberrations. RESULTS: Following exposure to 65Zn or gamma-irradiation, chromatid-type damage was more commonly observed than chromosome-type aberrations. The relationship between induced chromatid damage and gamma dose (to 3 Gy) was best fitted by a second-order polynomial function, while the activity response relationship for chromatid damage caused by 65Zn appeared to be best fitted by a straight line. Measurements of the uptake of 65Zn by cells showed that average concentrations within cells were about 100 times the concentration in the culture medium. Assuming uniform distribution of 65Zn within cells, with 36% in the nucleus, the dose was estimated as 0.70 Gy per MBq added 65Zn, with Auger electrons contributing most (93%) of the dose. Assuming that 20% of cellular zinc was localized in the nucleus, based on previous measurements, the dose to the nucleus was calculated as 0.44 Gy per MBq added 65Zn. RBE values for chromatid damage induced by 65Zn compared to gamma-radiation range from about 1 to 3 based on a uniform dose throughout the cell and from about 2 to 5 based on 20% of 65Zn in the cell nucleus. CONCLUSION: The observed radiotoxicity of 65Zn is consistent with its behaviour as an Auger-emitting radionuclide that is localized to some extent in the nucleus.

Adenocarcinoma↗

The 60Co gamma ray dose-response for chromosomal aberrations in human lymphocytes analysed by FISH; applicability to biological dosimetry.

PURPOSE: To investigate the in vitro dose-response for 60Co irradiated human lymphocytes assayed by FISH, and to consider how this may be applied to retrospective dosimetry. METHOD: Blood was irradiated with doses in the range 0.25-4.0 Gy. Cultured lymphocytes were scored for all stable and unstable aberrations involving painted chromosomes 2, 3 and 5 and, in addition, all unstable aberrations in the counterstained chromosomes. A pancentromeric probe was included. RESULTS: The relative numbers of painted and full genome dicentrics agreed well with the Lucas hypothesis for calculating genome equivalence. The involvement of each painted chromosome in exchanges agreed with their relative arm lengths. The dose-response relationship fitted well to the linear quadratic model; Y=(0.9 x 10(-2))D+(6.5 x 10(-2))D2 where D is the dose in Gy for the incidence Y, of all one plus two-way translocations in all cells corrected for genome equivalence. Complex rearrangements also became more frequent with increasing dose. A correlation was noted between the distributions of dicentrics and translocations among the cells and this was entirely due to complexes. CONCLUSIONS: For retrospective dosimetry it is recommended to use an in vitro dose-response for apparently simple translocations in stable (Cs) cells. To date, acute linear yield coefficients from FISH data carry statistical uncertainties too large for useful application to retrospective dosimetry of persons exposed to chronic or low doses. As an interim measure it is suggested that one may derive a linear term from full genome dicentrics corrected by a factor representing the translocation to dicentric ratio.

Cells, Cultured↗

Simple chromosome exchanges are not linear with dose.

PURPOSE: To check whether simple chromosome exchanges are linearly related to radiation dose. MATERIALS AND METHODS: Go-irradiated lymphocytes were cultured to produce metaphase preparations. Chromosomes 1 and 2 were painted different colours and the remaining chromosomes counterstained. Cells containing a colour junction involving both chromosomes 1 and 2 were scored fully, so that simple and complex rearrangements were distinguished. RESULTS: At doses of 2 Gy and below very few complex rearrangements were seen. About 90% of exchanges were simple. At these doses the linear component of the dose-effect curve accounts on average for only approximately 30% of the observed yield. CONCLUSIONS: There is a square-law dose component to the yield of simple exchanges in addition to the linear term.

Cells, Cultured↗

Neutron RBE values and their relationship to judgements in radiological protection.

This review traces the history of radiological protection judgements concerning the relative biological effectiveness (RBE) for neutrons and quality factor. The basis of the different views coming from the International Commission on Radiological Protection (ICRP) and the International Commission on Radiation Units and Measurements (ICRU) is explained. A review of present-day information on neutron RBE relevant to judgements for radiological protection purposes is presented. It is argued that variations in neutron RBE measurements are large so that for practical purposes pragmatic judgements need to be made. It is further suggested that no inconsistency arises if different judgements are made for different purposes. However, this would require some resolution of the contrasting views of ICRP and ICRU.

Animals↗

Comparison of dose-response curves for chromosomal aberrations established by chromosome painting and conventional analysis.

PURPOSE: To establish 60Co gamma-ray dose-response curves for dicentrics and translocations visualized by chromosome painting and for dicentrics analysed after conventional solid staining. MATERIALS AND METHODS: Analysis of chromosomal aberrations was performed on peripheral blood lymphocytes obtained from 48 h old cultures of irradiated whole blood. Dicentrics were scored from Giemsa-stained preparations, and bi-coloured dicentrics and translocations after FISH painting of chromosomes 1, 2 and 4. RESULTS: Equal frequencies of complete dicentrics and translocations, where both members of the exchanges were seen, were observed in the chromosome painting analysis at all doses, resulting in similar calibration curves. Due to differences in scoring criteria, dicentrics scored in conventionally Giemsa-stained slides agreed better with data for total than for complete exchanges. Donor differences for translocations at the control level and at low doses were seen and large uncertainty surrounds the linear component of the dose-response for total translocations. CONCLUSIONS: Dose reconstruction of past exposures in cases of low doses is very dependent on the linear coefficient of the curve. Results indicate that total translocations would give less reliable dose estimates and therefore complete translocations are preferred.

Adult↗

Accidental intake of tritiated water: a cytogenetic follow-up case on translocation stability and dose reconstruction.

PURPOSE: To examine by fluorescence in situ hybridization (FISH) chromosomal translocations in a person who, 11 years previously, had accidentally incorporated tritiated water. To compare the resultant estimate of radiation dose with contemporary dosimetry made by urine analysis and dicentric chromosome scoring. MATERIALS AND METHODS: Blood lymphocytes were shared by two laboratories each performing the FISH analysis using different chromosome probe combinations. Doses were calculated by reference to an in vitro calibration curve produced in one of the laboratories. RESULTS: Good agreement in translocation yields was found by the two laboratories. Comparing the yields with the dicentric frequency obtained shortly after the accident and with a translocation frequency measured 6 years post exposure showed good agreement between all measurements. This indicates essentially perfect stability for translocations over an 11 year period in this individual. CONCLUSIONS: Dose reconstruction based on FISH-measured translocations showed good agreement with the dose estimated from initial dicentric measurements and from measurements of tritium in urine. Because of the extensive initial dosimetry performed on this individual, who received a uniform whole-body irradiation, the case serves as an excellent test for the use of FISH-measured translocations for retrospective biodosimetry.

Chromosomes, Human↗

Risks from ionising radiation: deterministic effects.

This paper is a shortened version of an NRPB document that reviewed the deterministic effects on human health likely to arise from serious overexposure to ionising radiation. Little new primary information on deterministic effects has become available in recent years. However, advances in techniques for data analysis have been made, particularly in describing the sigmoid dose-effect relationships, effects of dose rate and radiation quality. These are presented in a form suitable for use in modelling the consequences to populations of serious radiological incidents.

Dose-Response Relationship, Radiation↗

Chromosome aberrations in Syrian hamsters following very low radiation doses in vivo.

This paper addresses a report of a large increase (approximately 6- to 11-fold) in chromosome aberrations in lymphocytes of persons in Salzburg attributed to their exposure to fallout from the Chernobyl cloud. Their additional exposure, approximately 0.3 mGy in 1 year, comprised about a 30% increase in their normal background radiation dose. The report has attracted considerable attention because, if correct, it seriously challenges assumptions of linearity in the low-dose response for chromosomal damage and, by implication, the linear, no-threshold hypothesis for risk of induced cancer. An experiment has been carried out with Syrian hamsters treated with caesium-137 to produce a range of doses comparable with those calculated for the persons in Salzburg. No significant elevation in lymphocyte aberration yields was found in the hamsters, thus arguing against the conclusions of the Salzburg study.

Animals↗

The influence of track structure on the understanding of relative biological effectiveness for induction of chromosomal exchanges in human lymphocytes.

A biophysical model has been applied to describe the production of exchange chromosomal aberrations (dicentrics) in human lymphocytes by radiations of different qualities. The model includes a detailed description of the energy deposition pattern in the form of computer-generated tracks. Energy deposition events are further converted to DNA double-strand breaks (DSBs). Formation of chromosomal exchanges is modeled in competition with repair in a distance-dependent manner with breaks in proximity being most likely to interact. We demonstrate that an assumption of an RBE > 1 for production of DSBs at higher LET leads to a significant increase with LET of both the linear and the quadratic coefficients of the dose response for exchange formation. The latter is not supported experimentally and argues against high RBE values for production of DSBs, at least for those breaks involved in chromosomal exchanges. Assuming that the RBE for production of DSBs is unity, the calculated dose-response curves conformed to experimental data for 60Co gamma rays, 250 kVp X rays and 8.7 MeV protons. The linear coefficient for 23.5 MeV 3He ions is underpredicted. The model predicts that a quadratic term in the dose response for exchange aberrations should be observed at LET values of 20-30 keV/microm. The curvature is not observed experimentally, and the contradiction is discussed.

Alpha Particles↗