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T Straume

Publications and source records attributed to T Straume.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1993

Translocations between two specific human chromosomes detected by three-color "chromosome painting".

Translocations between two specific chromosomes are important markers for many human malignancies. Previously, the detection of translocations involving random breakpoints between two specific chromosomes could only be accomplished by banding techniques, which are severely labor intensive and require highly trained technicians. The three-color chromosome painting approach described in this paper was developed in our laboratory to detect translocations between two specific human chromosomes rapidly and accurately, while simultaneously revealing the nonhybridized chromosomes. Because this method efficiently detects translocations involving breakpoints anywhere on the targeted chromosomes, it is ideal as a screening tool for chromosome-specific translocations.

Chromosomes, Human↗
PubMed1992

Rapid translocation frequency analysis in humans decades after exposure to ionizing radiation.

This paper presents an analysis of the utility of fluorescence in situ hybridization (FISH) with whole-chromosome probes for measurement of the genomic frequency of translocations found in the peripheral blood of individuals exposed to ionizing radiation. First, we derive the equation: Fp = 2.05fp(1-fp)FG, relating the translocation frequency, Fp, measured using FISH to the genomic translocation frequency, FG, where fp is the fraction of the genome covered by the composite probe. We demonstrate the validity of this equation by showing that: (a) translocation detection efficiency predicted by the equation is consistent with experimental data as fp is changed; (b) translocation frequency dose-response curves measured in vitro using FISH agree well with dicentric frequency dose-response curves measured in vitro using conventional cytogenetic procedures; and (c) the genomic translocation frequencies estimated from FISH measurements for 20 Hiroshima A-bomb survivors and four workers exposed to ionizing radiation during the Y-12 criticality accident are approximately the same as the translocation frequencies measured using G-banding. We also show that translocation frequency dose response curves estimated using FISH are similar for Hiroshima A-bomb survivors and for first division lymphocytes irradiated in vitro. We conclude with a discussion of the potential utility of translocation frequency analysis for assessment of the level of acute radiation exposure independent of the time between analysis and exposure.

Accidents↗
PubMed1992

Biodosimetry for a radiation worker using multiple assays.

Four state-of-the-art biodosimeters--GPA mutations, chromosome translocations, micronuclei, and dicentrics--were used to evaluate a radiation worker who believed that the official dosimetry records substantially underestimated his actual dose. Dosimetry records indicated that the worker received 0.56 Sv during a 36-y employment history, always within the dose limits. In contrast, the worker believed that his dose equivalent may have been more than 2.5 Sv because much of the exposure was received during the early days of health physics when dosimetry capabilities and practices were not as good as they are today. Because there are no biodosimetric assays that have been fully validated for the long-term low-level exposures received by the worker, we did not expect to obtain particularly useful point-estimates of dose. However, because the discrepancy between the dosimetry records and the worker's belief was so large, we believed that biodosimetry using multiple assays together with probabilistic assessment of the uncertainties would provide useful insight. Results showed that the frequencies of chromosome translocations and GPA mutations (stable biodosimeters) were significantly elevated when compared with those for unexposed controls. Our analysis suggests that dose-equivalent estimates in the approximately 0.4 to approximately 2 Sv range (which include the value in the dosimetry records) cannot be confidently excluded at this time based on biodosimetry; however, a value greater than 2.5 Sv appears unlikely. Important new information on the temporal stability of chromosome translocations is also presented.

Chromosome Aberrations↗
PubMed1992

Neutron discrepancies in the DS86 Hiroshima dosimetry system.

More than a decade has passed since a complete revision was initiated of the radiation doses received by survivors of the Hiroshima and Nagasaki atomic bombings. The new dosimetry system (DS86) was completed in 1986 and adopted shortly thereafter. Overall, DS86 was noted to be a clear improvement over the old dosimetry system. However, based on limited validation measurements, troublesome inconsistencies were suggested for neutrons. Since 1986, a substantial number of additional neutron activation measurements have been made in mineral and metal samples from Hiroshima. Importantly, a large number of measurements have now been made at distances beyond 1 km. Here, inconsistencies between neutron activation measurements and DS86 calculations for Hiroshima are examined using all available measurement data, including new measurements for 36Cl which extend the measurement range to more than 1.7 km from the epicenter, and Monte Carlo modeling calculations for each sample measured. Results show that thermal neutron activation measured beyond approximately 1 km in Hiroshima (at distances most relevant for radiation-risk evaluation) is two to 10, or more, times higher than that calculated based on DS86. Similar trends observed when comparing results by several independent measurement laboratories, using different analytical methods, suggest that the DS86 calculations for low-energy neutrons are in error. Because of the importance of the Hiroshima data in radiation risk evaluation, this large discrepancy is in need of resolution.

Japan↗
PubMed1991

Measurement of neutron-induced genetic damage in mouse immature oocytes.

Recent experimental evidence concerning the nature of radiosensitive targets in mouse immature (resting) oocytes has led to new experimental designs that permit measurement of radiation-induced genetic damage in these important cells. We have previously reported initial results of the detection of genetic damage in mouse immature oocytes using monoenergetic 0.43-MeV neutrons. Here we provide a full report of our data and compare the genetic sensitivity of immature oocytes with those measured by others for maturing oocytes. Until recently, all attempts to detect radiation-induced genetic damage in mouse immature oocytes had failed. This appears to have been because the radiation types and modes of dose delivery used in those studies did not sufficiently spare the hypersensitive lethality target (the plasma membrane) while at the same time deposit enough dose in DNA to produce detectable mutation. Recoil protons from 0.43-MeV neutrons produce short ionization tracks (2.6 micron mean) and can therefore deposit energy in the DNA without simultaneously traversing the plasma membrane. Using these particles, we have obtained dose-response relationships for both chromosome aberrations and dominant lethal mutations in oocytes from females irradiated 8-12 weeks earlier, when oocytes were immature. Results suggest that the intrinsic mutational sensitivity of mouse immature oocytes is not very different from that of maturing oocytes.

Age Factors↗
PubMed1991

Novel biodosimetry methods applied to victims of the Goiânia accident.

Two biodosimetric methods under development at the Lawrence Livermore National Laboratory were applied to five persons accidentally exposed to a 137Cs source in Goiânia, Brazil. The methods used were somatic "null" mutations at the glycophorin A locus detected as missing proteins on the surface of blood erythrocytes and chromosome translocations in blood lymphocytes detected using fluorescence in-situ hybridization. Biodosimetric results obtained approximately 1 y after the accident using these new and largely unvalidated methods are in general agreement with results obtained immediately after the accident using dicentric chromosome aberrations. Additional follow-up of Goiânia accident victims will 1) help provide the information needed to validate these new methods for use in biodosimetry and 2) provide independent estimates of dose.

Accidents↗
PubMed1991

Hiroshima-like neutrons from A-bomb replica: physical basis for their use in biological experiments.

The lineal energy distribution and several other dosimetric parameters were measured for the neutrons emitted from a replica of the Hiroshima bomb to determine their usefulness in biological experiments designed to estimate the effectiveness of actual Hiroshima neutrons. The "Little-Boy" replica (LBR) was constructed at the Los Alamos National Laboratory in support of the recent atomic-bomb dose reevaluation and was made of identical materials and had nearly identical dimensions and geometry as the Hiroshima bomb. However, the LBR was operated as a steady-state nuclear reactor, which permitted measurements under controlled conditions. Detailed dosimetric measurements and calculations were made at distances of up to 2.1 m from the center of the LBR uranium core. At these distances, the in-air kerma was approximately 97% from neutrons and kerma rates were shown to be particularly useful for biological experiments (up to approximately 7 Gy/h was possible). Quantitative intercomparisons of neutron energy spectra, lineal energy distributions, and measured cytogenetic results for several fission-neutron sources indicate that Hiroshima and LBR neutrons should be of similar biological effectiveness. Based on these evaluations, and cytogenetic results for LBR neutrons reported in a companion paper (this issue), it is estimated that Hiroshima neutrons were 20 to 30% more effective than the fission neutrons commonly used in radiobiology.

Neutrons↗
PubMed1991

Biological effectiveness of neutrons from Hiroshima bomb replica: results of a collaborative cytogenetic study.

The effectiveness of neutrons from a facsimile of the Hiroshima bomb was determined cytogenetically. The "Little-Boy" replica (LBR), assembled at Los Alamos as a controlled nuclear reactor for detailed physical dosimetry, was used. Of special interest, the neutron energy characteristics (including lineal energy) measured 0.74 m from the LBR were remarkably similar to those calculated for the 1945 Hiroshima bomb at 1 to 2 km from the hypocenter, as shown in a companion dosimetric paper (Straume, et al., Radiat. Res. 128, 133-142 (1991)). Thus we examine here the effectiveness of neutrons closely resembling those that the A-bomb survivors received at Hiroshima. Chromosome aberration frequencies were determined in human blood lymphocytes exposed in vitro to graded doses of LBR radiation (97% neutrons, 3% gamma rays). Vials of blood suspended in air at distances up to 2.10 m from the center of the LBR uranium core received doses ranging from 0.02 to 2.92 Gy. The LBR neutrons (E approximately 0.2 MeV) produced 1.18 dicentrics and rings per cell per Gy. They were more effective than the higher-energy fission neutrons (E approximately 1 MeV) commonly used in radiobiology. The maximum RBE (RBEM) of LBR neutrons at low doses is estimated to be 60 to 80 compared to 60Co gamma rays and 22 to 30 compared to 250-kVp X rays. These results provide a quantitative measurement of the biological effectiveness of Hiroshima-like neutrons.

Adult↗
PubMed1991

Applications of fluorescence in situ hybridization in biological dosimetry and detection of disease-specific chromosome aberrations.

Dual color FISH with whole chromosome and pan-centromere probes facilitates rapid detection of stable structural aberrations such as translocations. This approach should allow analysis of translocations for assessment of genetic damage at long times after exposure or as a result of chronic exposure during a long period of time. Multi-color FISH with locus specific probes allows assessment of the frequency of cells carrying specific aberrations known to be associated with tumorigenesis, analysis of the series of genetic changes that occur during tumor evolution and correlation between genotype and phenotype. The power of FISH for analysis of random and tumor related events will increase steadily as informative probes are developed during the course of the International Human Genome Project.

Chromosome Aberrations↗
PubMed1989

Size of lethality target in mouse immature oocytes determined with accelerated heavy ions.

Mouse immature oocytes were irradiated in vivo with highly charged, heavy ions from the Bevalac accelerator at the Lawrence Berkeley Laboratory. The particles used were 670-MeV/nucleon Si14+, 570-MeV/nucleon Ar18+, and 450-MeV/nucleon Fe26+. The cross-sectional area of the lethality target in these extremely radiosensitive cells was determined from fluence-response curves and information on energy deposition by delta rays. Results indicate a target cross-section larger than that of the nucleus, one which closely approximates the cross-sectional area of the entire oocyte. For 450-MeV/nucleon Fe26+ particles, the predicted target cross-sectional area is 120 +/- 16 microns2, comparing well with the microscopically determined cross-sectional area of 111 +/- 12 microns2 for these cells. The present results are in agreement with our previous target studies which implicate the oocyte plasma membrane.

Animals↗
PubMed1989

Rapid human chromosome aberration analysis using fluorescence in situ hybridization.

We have used in situ hybridization of repeat-sequence DNA probes, specific to the paracentromric locus 1q12 and the telomeric locus 1p36, to fluorescently stain regions that flank human chromosome 1p. This procedure was used for fast detection of structural aberrations involving human chromosome 1p in two separate experiments. In one, human lymphocytes were irradiated with 0, 0.8, 1.6, 2.4 and 3.2 Gy of 137Cs gamma-rays. In the other, human lymphocytes were irradiated with 0, 0.09, 0.18, 2.0, 3.1 and 4.1 Gy of 60Co gamma-rays. The frequencies (per cell) of translocations and dicentrics with one breakpoint in 1p and one elsewhere in the genome were determined for cells irradiated at each dose point. These frequencies both increased with dose, D, in a linear-quadratic manner. The delta, alpha, and beta coefficients resulting from a fit of the equation f(D)=delta + alphaD + betaD2 to the translocation frequency dose-response data were 0.0025, 0.0027 and 0.0037 for 137Cs gamma-rays, and 0.0010, 0.0041, and 0.0057 for 60Co gamma-rays. The delta, alpha, and beta coefficients resulting from a fit to the dicentric frequency dose-response data were 0.0005, 0.0010 and 0.0028 for 137Cs gamma-rays and 0.0001, 0.0002 and 0.0035, for 60Co gamma-rays. Approximately 32,000 metaphase spreads were scored in this study. The average analysis rate was over two metaphase spreads per minute. However, an experienced analyst was able to find and score one metaphase spread every 10s. The importance of this new cytogenetic analysis technique for biological dosimetry and in vivo risk assessment is discussed.

Cesium Radioisotopes↗
PubMed1987

Neutron RBEs and the radiosensitive target for mouse immature oocyte killing.

The highly radiosensitive immature oocytes of mice were irradiated in vivo with graded doses of 252Cf fission radiation, 0.43- or 15-MeV neutrons, or 60Co gamma rays. Comparisons of oocyte survival for neutrons and for gamma rays demonstrate that neutron RBEs for the killing of these important cells do not reach the high values (30-50 or more) at low doses observed for several other biological end points. Rather, neutrons differ little in effectiveness from gamma rays in killing these extremely sensitive murine oocytes. For 0.43-MeV neutrons, RBEs obtained from fitted survival curves reach only 1.7 at 0.1 rad. For 15-MeV neutrons, they are not significantly different from 1 at any dose tested (lowest, 4.5 rad). For 252Cf fission neutrons (E = 2.15 MeV), RBEs are intermediate between those for 0.43- and 15-MeV neutrons. For all neutron energies tested, the RBEs are particularly low in the juvenile period, a time when murine immature oocytes are especially radiosensitive. With exposure just prior to birth, however, when these cells are much less easily killed, higher, more usual RBEs are found. The minimum size of the lethality target in mouse immature oocytes, estimated from the inactivation constant for 0.43-MeV neutrons and microdosimetric values, is larger than the nucleus but not larger than the cell. This and related analytical considerations suggest that the hypersensitive target in these particular oocytes is the plasma membrane, a finding which is in excellent accord with results from other experiments using different, contrasting radiations and dose deliveries (accelerated Si14+ ions, gamma rays, and beta rays from 3HOH compared with those from [3H]thymidine).

Animals↗
PubMed1986

Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization.

This report describes the use of fluorescence in situ hybridization for chromosome classification and detection of chromosome aberrations. Biotin-labeled DNA was hybridized to target chromosomes and subsequently rendered fluorescent by successive treatments with fluorescein-labeled avidin and biotinylated anti-avidin antibody. Human chromosomes in human-hamster hybrid cell lines were intensely and uniformly stained in metaphase spreads and interphase nuclei when human genomic DNA was used as a probe. Interspecies translocations were detected easily at metaphase. The human-specific fluorescence intensity from cell nuclei and chromosomes was proportional to the amount of target human DNA. Human Y chromosomes were fluorescently stained in metaphase and interphase nuclei by using a 0.8-kilobase DNA probe specific for the Y chromosome. Cells from males were 40 times brighter than those from females. Both Y chromosomal domains were visible in most interphase nuclei of XYY amniocytes. Human 28S ribosomal RNA genes on metaphase chromosomes were distinctly stained by using a 1.5-kilobase DNA probe.

Aneuploidy↗