Biomedical subjects

T Straume

Publications and source records attributed to T Straume.

At least 19 recordsLinked to original sources

PubMed1997

Transmitted proliferation disadvantage from mouse oocytes labeled in vivo with [3H]thymidine: radiosensitive target considerations.

This study was conducted to test the hypothesis that a nuclear target is involved in the embryonic cell proliferation disadvantage transmitted by irradiated mouse oocytes and detected by the chimera assay. In this assay, the cells from the irradiated embryo exhibit a competitive cell proliferation disadvantage when they are challenged by direct cell-cell contact with cells from a normal embryo in an aggregation chimera. Here, six pregnant CD-1 mice received a total of 1.85 TBq tritiated thymidine (TdR) delivered by multiple intraperitoneal injections during days 13-15 postconception. Six more pregnant mice were sham-injected to provide control embryos. Sixty randomly selected female progeny were mated at 47 days of age and their 4-cell embryos tested in the chimera assay. The mean proliferation ratio (PR, number of cells from the experimental embryo divided by total cell number of the chimera) for experimental chimeras was 0.45 +/- 0.02 SE (n = 43), which was significantly less than the mean PR of 0.49 +/- 0.01 SE (n = 47; p = 0.02) for control chimeras. This entire experiment was repeated, with similar results. A comparison for TdR confined to the nucleus (i.e., mean beta-ray range is only 0.7 microm) with the relationship for uniform irradiation by 137Cs gamma-rays demonstrates that these two very different modes of dose delivery produce essentially identical PRs. These results in vivo suggest a nuclear DNA target for embryonic cell proliferation disadvantage consistent with our previous findings in vitro.

Animals↗

PubMed1997

Emerging technological bases for retrospective dosimetry.

In this article we discuss examples of challenging problems in retrospective dosimetry and describe some promising solutions. The ability to make measurements by accelerator mass spectrometry and luminescence techniques promises to provide improved dosimetry for regions of Belarus, Ukraine and Russian Federation contaminated by radionuclides from the Chernobyl accident. In addition, it may soon be possible to resolve the large neutron discrepancy in the dosimetry system for Hiroshima through novel measurement techniques that can be used to reconstruct the fast-neutron fluence emitted by the bomb some 51 years ago. Important advances in molecular cytogenetics and electron paramagnetic resonance measurements have produced biodosimeters that show potential in retrospective dosimetry. The most promising of these are the frequency of reciprocal translocations measured in chromosomes of blood lymphocytes using fluorescence in situ hybridization and the electron paramagnetic resonance signal in tooth enamel.

Animals↗

PubMed1997

Determination of iodine in milk and oyster tissue samples using combustion and peroxydisulfate oxidation.

Two methods are described for the preparation of samples for total iodine measurement in biological matrices. In the first method, the samples were combusted in a stream of oxygen to release iodine that, subsequently, was trapped in a solution as iodide. The second method is a new approach in which the samples were oxidized in a basic solution of peroxydisulfate. In this case, the iodine was retained in solution as iodate. Total iodine was measured by gas chromatographic analysis of the 2-iodopentan-3-one derivative. The methods were tested using Standard Reference Materials (SRMs) 1549 Non-Fat Milk Powder, and 1566a and 1566 Oyster Tissue. Also, KI and KIO3 were used for testing the procedures. The results obtained for the SRMs, given as average +/- standard deviation in micrograms g-1, were: 3.39 +/- 0.14 and 3.40 +/- 0.23 for SRM 1549; 4.60 +/- 0.42 and 4.51 +/- 0.45 for SRM 1566a; and 2.84 +/- 0.16 and 2.76 +/- 0.06 for SRM 1566; values corresponding to combustion and wet oxidation, respectively. Overall, the absolute recoveries varied between 91 and 103%. These methods can also be used in the preparation of targets for the measurement of 129I using accelerator mass spectrometry.

Animals↗

PubMed1997

Impaired cell proliferation in mice that persists across at least two generations after paternal irradiation.

Irradiation of male F0 mice 6 to 7 weeks prior to mating causes significant changes in the proliferation of F1 and F2 embryonic cells. These changes are revealed as a competitive cell proliferation disadvantage in chimera assays when the affected embryo is paired with a normal embryo in an aggregation chimera. This effect has been observed previously to be transmitted to F1 embryos for absorbed doses from 0.01 to 1.0 Gy; 0.01 Gy is about 100-fold lower than detectable using conventional germline mutation assays. However, until now there has been no reported cross-generation heritability. We now report that this competitive cell proliferation disadvantage persists without degradation in the F2 generation of embryos when F0 males received 1.0 Gy from gamma irradiation 6 and 7 weeks prior to conception of F1 males.

Animals↗

PubMed1997

Issues in cytogenetic biological dosimetry: emphasis on radiation environments in space.

Issues central to the reliability of cytogenetic biodosimetry are presented. Although it now appears that cytogenetic biodosimetry can be used reliably to reconstruct radiation dose after acute, uniform whole-body exposure (albeit within certain dose ranges), additional data are required to fully validate cytogenetic biodosimetry for the protracted and complex exposure conditions in space. Approaches are presented that could be used to obtain the data necessary for validation. It also appears that the use of dicentric aberrations for biodosimetry on missions lasting several months or more may not be reliable because of the large variability observed among individuals in the rate of loss of cells with dicentrics, making back-extrapolations uncertain. This may be testable, however, by comparing the results for dicentrics and translocations obtained by biodosimetry with the radiation dosimetry obtained on board the spacecraft. In addition to these and several other issues, estimates are provided of the current limitations of detection of dicentrics and reciprocal translocations.

Aerospace Medicine↗

PubMed1996

Mouse immature oocytes irradiated in vivo at 14-days of age and evaluated for transmitted effects using the aggregation embryo chimera assay.

A previous study using the mouse-preimplantation-embryo-chimera assay demonstrated a reproducible transmitted effect (proliferation disadvantage observed in early embryos) from females irradiated as 49-day-old adults using 0.15 Gy of gamma rays and then mated seven weeks later, i.e., embryos were from oocytes that were immature at time of irradiation. Because mouse immature oocytes are known to be much more radiosensitive to cell killing in juveniles than in adults, a follow-on study was performed here using 14-day-old juvenile mice. In contrast to adults, the exposure of juveniles to 0.15 Gy of gamma rays did not result in a detectable transmitted proliferation disadvantage when animals were mated 7 or 12 weeks later. This observation is discussed in light of previous studies on mouse immature oocytes and embryo chimeras.

Age Factors↗

PubMed1996

Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys.

Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

Animals↗

PubMed1996

The feasibility of using 129I to reconstruct 131I deposition from the Chernobyl reactor accident.

Radioiodine released to the atmosphere from the accident at the Chernobyl nuclear power station in the spring of 1986 resulted in large-scale thyroid-gland exposure of populations in Ukraine, Belarus, and Russia. Because of the short half life of 131I (8.04 d), adequate data on the intensities and patterns of iodine deposition were not collected, especially in the regions where the incidence of childhood-thyroid cancer is now increasing. Results are presented from a feasibility study that show that accelerator-mass-spectrometry measurements of 129I (half life 16 x 106 y) in soil can be used to reconstruct 131I-deposition density and thus help in the thyroid-dosimetry effort that is now urgently needed to support epidemiologic studies of childhood-thyroid cancer in the affected regions.

Cesium Radioisotopes↗

PubMed1995

Dose-response curve for chromosome translocations measured in human lymphocytes exposed to 60Co gamma rays.

Chromosome painting was employed to measure frequencies of reciprocal translocations in human lymphocytes induced by 60Co gamma rays, with emphasis on low doses. Translocations and dicentrics were distinguished by use of a pan-centromeric probe. A total of 41,151 metaphases were analyzed at doses below 0.2 Gy. The linear "take-off" slope of the linear-quadratic dose-response curve for translocations, i.e., the alpha coefficient, was measured to be 0.023 +/- 0.005 translocations per cell per Gy. This alpha coefficient is more precise than previously measured. Because the alpha coefficient is the dominant contributor to the translocation frequency induced by low-level exposures, the results presented here will substantially reduce uncertainties in biodosimetry estimates obtained for stable translocations.

Biophysical Phenomena↗

PubMed1995

High-energy gamma rays in Hiroshima and Nagasaki: implications for risk and WR.

Based on the DS86 dosimetry system, nearly all of the dose to survivors of the atomic bombings of Hiroshima and Nagasaki was due to unusually high-energy gamma rays, predominantly in the 2- to 5-MeV range. These high energies resulted in part from neutron capture gamma rays as the bomb neutrons penetrated large distances of air. Because of the inverse relationship between energy and biological effectiveness, these high-energy gamma rays are expected to be substantially less effective in producing biological damage than the radiations commonly used in radiobiology and risk assessment. This observation has implications for radiation protection and risk assessment.

Gamma Rays↗

PubMed1994

Radiosensitive target in the early mouse embryo exposed to very low doses of ionizing radiation.

We exposed mouse preimplantation embryos in vitro to either tritiated water (HTO) or tritiated thymidine (TdR) to determine whether the radiosensitive target was nuclear or extranuclear for embryonic cell proliferation disadvantage in the mouse embryo chimera assay. 8-cell embryos were incubated in either HTO or TdR for 2 h and paired with non-irradiated control embryos to form chimeras. Chimeras were cultured for an average of 20.2 h to allow for 2-3 cell cycles and then partially dissociated to obtain the number of progeny cells contributed by the two partner embryos for each chimera. These values were expressed as a "proliferation ratio" (number of cells from the irradiated embryo: total number of cells in the chimera). A ratio significantly less than 0.50 indicates that the experimental embryo expressed an embryonic cell proliferation disadvantage, which is the endpoint of this assay. The activity concentrations of HTO and TdR were adjusted so that both would deliver comparable mean absorbed nuclear doses during the combined initial 2-h irradiation incubation and subsequent 20.2 h chimera incubation periods. Although nuclear doses were comparable under these conditions, the extranuclear dose delivered by the uniformly distributed HTO was about 100 times greater than the extranuclear dose delivered by TdR for each given nuclear dose. Consequently, obtaining mean TdR proliferation ratios < or = mean HTO proliferation ratios would be evidence for a nuclear target while obtaining mean HTO proliferation ratios < mean TdR proliferation ratios would be evidence for an extranuclear target. TdR consistently produced lower mean proliferation ratios over a range of doses from 0.14 Gy to 0.43 Gy. Therefore, we conclude that the radiosensitive target for this endpoint is nuclear.

Animals↗

PubMed1994

Discrimination between leukaemia and non-leukaemia-related chromosomal abnormalities in the patient's lymphocytes.

The inability to measure precancer-related genetic damage accurately in blood cells of patients with leukemia or lymphoma has prevented the use in such patients of available biodosimetric methods to determine prior exposure to clastogenic agents. This is because a substantial amount of disease-related genetic damage appears in the blood cells of these patients, thus masking genetic damage that may have been caused prior to the disease. We describe a new approach that may be used to measure precancer-related chromosomal aberrations in such patients by totally separating the affected T lymphocytes from the malignant B lymphocytes. The approach employs stable chromosome translocations and will detect prior exposures above the detection limit of approximately 0.05-0.1 Gy. The utility of this approach is illustrated by using blood lymphocytes from a nuclear dockyard worker who claims his B cell leukaemia was induced by work-related radiation exposures. Blood lymphocytes were obtained after diagnosis of the disease, but prior to therapy, and measurements were made of the frequency of chromosomal abnormalities in PHA-stimulated lymphocytes without prior separation of T and B cells and in T lymphocytes after complete separation from B cells using a rosetting technique. Results show that the separation of T cells prior to PHA stimulation eliminates the cancer-related chromosomal damage and thus appears to facilitate biodosimetry of pre-cancer exposures in such patients.

Adult↗

PubMed1994

Non-cancer related chromosome translocation frequency measured from a leukemia patient's blood.

A new approach used to measure pre-cancer-induced genetic damage in a patient diagnosed as early B-precursor acute lymphoblastic leukemia, by totally separating the malignant B-lymphocytes and the normal T-lymphocytes is described. The lymphocytes separation by a rosetting method and chromosome translocation analysis using chromosome painting were employed. In the case presented here, the utility of this approach is illustrated using blood lymphocytes from a nuclear dockyard worker who claims that his leukemia was induced by work-related radiation exposures. Blood lymphocytes were obtained after diagnosis of the disease, but prior to therapy, and measurements made of (1) the translocation frequency in separated normal T-lymphocytes and (2) the translocation frequency in phytohemagglutinin (PHA) stimulated lymphocytes, which include a fraction of the malignant B cells. The approach described here makes possible biodosimetry of pre-cancer exposures in these patients and may provide the dosimetric information required to establish the "probability of causation" for the observed cancer.

B-Lymphocytes↗

PubMed1994

Neutrons confirmed in Nagasaki and at the Army Pulsed Radiation Facility: implications for Hiroshima.

Recent reports have clearly demonstrated that large discrepancies exist between neutron activation measured in Hiroshima and activation calculated using the current dosimetry system, DS86. The reports confirmed previous results for cobalt activation in Hiroshima that suggested problems, and this has spurred a joint U.S.-Japan effort to identify the source(s) of this discrepancy. Here, new results are presented that appear to eliminate both the measurements of neutron activation and the DS86 air-transport calculations as potential sources of the discrepancy in Hiroshima. Computer transport of DS86 fission neutrons through large distances of air was validated using concrete samples from Nagasaki and chloride detectors placed at selected distances from a bare uranium reactor. In both cases, accelerator mass spectrometry was used to measure thermal neutron activation via the reaction, 35Cl(n, gamma)36Cl (half-life, 301,000 years). Good agreement was observed between measurements of neutron activation and DS86 calculations for Nagasaki, as well as for the reactor experiment. Thus the large discrepancy observed in Hiroshima appears not to be due to uncertainties in air-transport calculations or in the activation measurements; rather, the discrepancy appears to be due to uncertainties associated with the Hiroshima bomb itself.

Chlorides↗

PubMed1993

Inherited effects from irradiated mouse immature oocytes detected in aggregation embryo chimeras.

Data obtained using the mouse-preimplantation-embryo-chimera assay are presented that show a transmitted effect following low-dose irradiation of immature oocytes in vivo. Six-week-old female mice were irradiated using 137Cs-gamma-rays (0.05 Gy, 0.15 Gy, and unexposed controls). At 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 weeks post exposure, the mice were mated and aggregation chimeras made from the 4-cell embryos. Three independent experiments have now been carried out, all showing a significant embryonic cell-proliferation disadvantage of the embryos obtained from the females treated 7 weeks previously, i.e., embryos from oocytes that were immature at the time of radiation exposure. No effect was detected at 1-6 weeks when embryos were obtained from maturing oocytes. Also, the effect was not seen at 8, 9, 10, 11, and 12 weeks post exposure. The implications of these results are discussed in the light of previous studies on mouse oocytes.

Animals↗

PubMed1993

A comparison of the yields of translocations and dicentrics measured using fluorescence in situ hybridization.

Chromosome aberration analysis using fluorescence in situ hybridization (FISH) methods without centromere-specific markers results in the misscoring of a substantial fraction of the dicentrics as translocations; that is, too many translocations and too few dicentrics are scored. Such misscoring has led to considerable confusion in the rapidly emerging literature on FISH-based cytogenetics. Here, we demonstrate that the problem is fully resolved when centromeric probes are used.

Chromosome Aberrations↗

PubMed1993

Tritium radiobiology and relative biological effectiveness.

During the past decade, a large number of radiobiological studies have become available for tritium--many of them focusing on the relative biological effectiveness of tritium beta rays. These and previous studies indicate that tritium in body water produces the same spectrum of radiogenic effects (e.g., cancer, genetic effects, developmental abnormalities, and reproductive effects) observed following whole-body exposure to penetrating radiations such as gamma rays and x rays. However, tritium beta rays are of greater biological effectiveness than gamma rays and x rays. For example, tritium in the oxide form is about 2 to 3 times more effective at low doses or low dose rates than gamma rays from 137Cs or 60Co. When tritium is bound to organic molecules, relative biological effectiveness values may be somewhat larger than those for tritium in oxide form. Tritium administered to animals or to cells in vitro as tritiated amino acids results in relative biological effectiveness values that appear similar to those obtained for tritium in oxide form; however, if administered as tritiated thymidine, the relative biological effectiveness values appear to be about two-fold higher. It is clear from the wealth of tritium data now available that relative biological effectiveness values for tritium beta rays are higher than the quality factor of unity generally used in radiation protection.

Humans↗

PubMed1993

Tritium risk assessment.

Estimates of the health risks in humans from low-level exposure to tritium are presented. The health risks considered are those for cancer, genetic effects, and developmental abnormalities from exposures in utero. Because direct risk information for these effects is not available from human exposures to tritium, the following approach was used. Excess risks for the effects given following low-level exposure to x rays or gamma rays were estimated from available human epidemiological data using appropriate dose-rate effectiveness factors. These human-risk estimates for low-level x rays or gamma rays were then multiplied by the appropriate best-estimate relative biological effectiveness for tritium, taking into account differences in effectiveness of comparison radiations. The resultant lifetime risk coefficients for low-level exposure to tritiated water are as follows. For cancer mortality, the most probable risk (50th percentile) is 81 x 10(-6) mGy-1 and the 90% confidence interval is 38 to 185 x 10(-6) mGy-1. For genetic effects in the first generation after exposure the risk is 7.9 x 10(-6) mGy-1, with a 90% confidence interval of 3.8 to 16.3 x 10(-6) mGy-1. For developmental effects from low-level tritiated water exposures in utero, the risk is uncertain but is estimated to be < 400 x 10(-6) mGy-1. The risks from exposure to organically bound tritiated molecules are estimated to range from values that are similar to those for tritiated water to about a factor of 2 higher.

Abnormalities, Radiation-Induced↗