Biomedical subjects

P A Hone

Publications and source records attributed to P A Hone.

6 recordsLinked to original sources

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↗

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↗

PubMed2002

The placental transfer of cerium: experimental studies and estimates of doses to the human fetus from 141Ce and 144Ce.

PURPOSE: To measure the transfer of cerium from mother to fetus in experimental animals and estimate doses to the human fetus following intakes of radioisotopes of Ce. MATERIALS AND METHODS: Cerium-141 in chloride solution was administered intravenously to rats at different stages of pregnancy (days 9.5, 12.5 or 18.5), and retention in the embryo/fetus and associated tissues was measured 3 days later in each case. Retention in rat fetal tissues on day 21.5 (shortly before birth) was also measured after administration of 141Ce chloride 1 month prior to conception or 141Ce citrate on day 18.5. Cerium-141 chloride was administered to guinea pigs on day 50 for measurements of fetal retention on day 57 (shortly before birth). RESULTS: Retention of 141Ce in the rat embryo/fetus, measured at 3 days after administration to the mother, increased from about 0.00002% of injected activity per embryo/fetus on day 12.5 to about 0.014% on day 21.5 of gestation. However, the relative concentrations of 141Ce in the embryo/fetus and mother (CF:CM ratio) were between 0.005 and 0.01 in each case. After 141Ce administration prior to conception, retention by the rat fetus on day 21.5 was substantially lower than after short-term administration. Comparison of retention of 141Ce on day 21.5 after administration on day 18.5 as either chloride or citrate showed similar levels in maternal tissues but greater transfer to the fetus (CF:CM ratio of 0.03). Retention in the guinea pig fetus in late gestation at 7 days after administration of (141)Ce chloride was about 0.05% injected activity per fetus, corresponding to a CF:CM ratio of about 0.02. CONCLUSION: These results and other published animal data have been used to specify CF:CM ratios for use in the calculation of doses to the human fetus. The values used were 0.05 for intakes during pregnancy and 0.01 for intakes prior to conception. Doses to the offspring after maternal ingestion of 141Ce or 144Ce are largely due to irradiation from activity in the maternal colon and are insensitive to CF:CM. After inhalation, however, absorption of Ce to blood is much greater and doses to the offspring are dominated by the contribution from activity in the fetus, and therefore dependent on the CF:CM ratio used.

Animals↗

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↗

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↗