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J E Moquet

Publications and source records attributed to J E Moquet.

At least 19 recordsLinked to original sources
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↗
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↗
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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
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↗
PubMed1988

Radiation induction of micronuclei in human lymphocytes.

An examination of the cytokinesis-blocked micronucleus technique confirmed its potential usefulness as a method of biological dosimetry for radiation accidents. Several advantages and disadvantages of the system are discussed. It has been demonstrated that under the conditions of these experiments, the blocking agent, cytochalasin B does not induce micronuclei or unstable chromosome aberrations. The induction of sister-chromatid exchanges proved just significant. Analysis of the dose response for 250 kVp X-rays indicates that although the Y = alpha D + beta D2 model fits the data, the relationship does not correspond to that for total aberration induction as might have been expected. The background frequency of micronuclei and the value of the alpha coefficient are higher than for total aberrations and the beta term is lower. This indicates that simple incorporation of acentric chromosome fragments into micronuclei may not wholly account for the phenomenon.

Adult↗
PubMed1988

In vitro induction of chromosomal aberrations in human lymphocytes, with and without boron 10, by radiations concerned in boron neutron capture therapy.

A beam consisting of mainly 24 keV neutrons has been constructed for radiobiological studies to evaluate the potential of these particles for treating deep tumours by the boron capture reaction. The induction of chromosomal aberrations in human lymphocytes in vitro was examined and a linear dose effect with a relative biological effectiveness similar to fission neutrons was obtained. For samples placed at depths in a plastic phantom the aberration yields declined with depth at a rate matching the fall in the sum of dose due to proton recoils and neutron capture in nitrogen 14. The presence of boron 10 at 30 micrograms ml-1 did not affect the aberration yield. By using the mixed sample method, the probability of interphase death or mitotic delay in cells crossed by an alpha particle or lithium-7 ion produced in the boron capture reaction was shown to be close to 1.0. Thus these cells are prevented from coming to mitosis in culture. The implications for boron capture therapy are that this filtered beam has a "high LET" effect which could lead to poor normal tissue sparing. However there may be a significant therapeutic advantage due to a high probability of killing tumour cells that have incorporated boron 10.

Boron↗