Biological effectiveness of fast neutrons with a mean energy of 22 MeV

Biological effectiveness of fast neutrons of a mean energy of 22 MeV obtained by the reaction d[50 MeV]----Be, measured by the death rate, was substantially lower than that of division spectrum neutrons of a mean energy of 1.2 MeV. LD50/30 of the division spectrum neutrons was within 2.57 +/- 0.07 Gy and that of 22 MeV fast neutrons 4.79 +/- 0.13 Gy. The RBE coefficient for the studied neutrons was 1.34 +/- 0.05 as estimated by LD50/30 and 1.5 +/- 0.1 as determined by D37 for a cell model of radiation affection.     

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.     

Analysis of results from a collaborative study of the dominant lethal assay

A dominant lethal (DL) mutation is a genetic change that results in the death of the conceptus that inherits it. The assya is normally carried out in mice and the production of DL mutation by the test chemical is characterised by an increase in non-viable embryos.A distinct advantage of the DL assay is that it is an in vivo, mammalian, germ cell assay and is therefore pertinent to the fundamental question of chemical mutagenesis, i.e.: is a chemical likely to produce genetic changes that can be transferred to the offspring? The two principal criticisms of the assay are that the main type of genetic damage it detects is chromosomal breakage that leads to the conceptus, and that the assay is considered to be relatively insensitive.The Association of the British Pharmaceutical Industry (ABPI) Working Party on Mutagenicity was established in 1974. Its principal objective was to consider the problem of mutagenicity and associated matters in relation to the development of new medicines and to make recommendations and proposals for collaborative work if indicated. The dominant lethal assay is one of several tests for mutagenicity chosen for evaluation by collaborative study. The objective of the collaborative study was to gain more information about the validity and dependability of the dominant lethal assay.The present report concerns an analysis of the differences between compounds, laboratories and statistical methods utilising the data from the collaborative study.     

Experimental derivation of relative biological effectiveness of A-bomb neutrons in Hiroshima and Nagasaki and implications for risk assessment

Epidemiological data on the health effects of A-bomb radiation in Hiroshima and Nagasaki provide the framework for setting limits for radiation risk and radiological protection. However, uncertainty remains in the equivalent dose, because it is generally believed that direct derivation of the relative biological effectiveness (RBE) of neutrons from the epidemiological data on the survivors is difficult. To solve this problem, an alternative approach has been taken. The RBE of polyenergetic neutrons was determined for chromosome aberration formation in human lymphocytes irradiated in vitro, compared with published data for tumor induction in experimental animals, and validated using epidemiological data from A-bomb survivors. The RBE of fission neutrons was dependent on dose but was independent of the energy spectrum. The same RBE regimen was observed for lymphocyte chromosome aberrations and tumors in mice and rats. Used as a weighting factor for A-bomb survivors, this RBE system was superior in eliminating the city difference in chromosome aberration frequencies and cancer mortality. The revision of the equivalent dose of A-bomb radiation using DS02 weighted by this RBE system reduces the cancer risk by a factor of 0.7 compared with the current estimates using DS86, with neutrons weighted by a constant RBE of 10.     

A chromosome study of 6-thioguanine-resistant mutants in T lymphocytes of Hiroshima atomic bomb survivors

Cytogenetic characterizations were made of lymphocyte colonies established from somatic mutation assays for 6-thioguanine (TG) resistance in Hiroshima atomic bomb survivors. G-banded chromosomes were analyzed in both TG-resistant (TGr) and wild-type colonies. Included were 45 TGr and 19 wild-type colonies derived from proximally exposed A-bomb survivors, as well as colonies from distally exposed control individuals who did not receive a significant amount of A-bomb radiation (18 TGr and 9-wild type colonies). Various structural and numerical chromosome abnormalities were observed in both TGr and wild-type colonies. Aberrations of the X chromosome, on which the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus is present, were found in 6 colonies: 2 resistant colonies from controls (45,X/46,XX; 46,X,ins(X)), 3 resistant colonies (45,X/46,XX/46,X, + mar; 46,X,t(Xq +;14q-); 46,Y,t(Xq-;5q +)), and 1 wild-type colony (45,X/47,XXX) from proximally exposed persons. In cases with exchange aberrations, each of the break points on the X chromosome was situated proximally to band q26 where the HPRT locus is known to be assigned. DNA-replicating patterns were also studied, and it was found that abnormal X chromosomes showed early replicating patterns, while normal X chromosomes showed late replicating patterns.     

The F value for chromosome aberrations in atomic bomb survivors does not provide evidence for a primary contribution of neutrons to the dose in Hiroshima.

Brenner and Sachs (Radiat. Res. 140, 134-142, 1994) proposed that the ratio of interchromosomal to intrachromosomal exchanges, termed the F value, can be a cytogenetic fingerprint of exposure to radiations of different linear energy transfer (LET). Using published data, they suggested that F values are over 10 for low-LET radiations and approximately 6 for high-LET radiations. Subsequently, as F values for atomic bomb survivors were reported to be around 6, Brenner suggested that the biological effects of atomic bomb radiation in Hiroshima are due primarily to neutrons. However, the F values used for the survivors were means from individuals exposed to various doses. As the F-value hypothesis predicts a radiation fingerprint at low doses, we analyzed our own data for the survivors in relation to dose. G-banding data for the survivors showed F values varying from 5 to 8 at DS86 doses of 0.2 to 5 Gy in Hiroshima and around 6 in Nagasaki with no evidence of a difference between the two cities. The results are consistent with our in vitro data that the F values are invariably around 6 for X and gamma rays at doses of 0.5 to 2 Gy as well as two types of fission-spectrum neutrons at doses of about 0.2 to 1 Gy. Thus, apart from a possible effect at even lower doses, current data do not provide evidence to support the proposition that the biological effects of atomic bomb radiation in Hiroshima are caused mainly by neutrons.     

Thermoluminescence dosimetry of gamma rays from the atomic bomb at Hiroshima using the predose technique

Thermoluminescence dosimetry measurements of gamma rays produced by the atomic bomb in Hiroshima were made by the predose technique using eight ceramic samples collected from five buildings located at distances between 1271 and 2051 m from the hypocenter. The results of our measurements are compared to both the newer dose estimates (Dosimetry System 1986) and older dose estimates (Tentative 1965 Doses) for survivors of the Hiroshima atomic bomb. In comparison with the older estimates, our results are larger by a factor of 2.3 at 1271 m and 3.9 at 2051 m. Our results and the newer estimates for Hiroshima differ by a factor of only 1.14 +/- 0.16 on the average.     

Effective dose of A-bomb radiation in Hiroshima and Nagasaki as assessed by chromosomal effectiveness of spectrum energy photons and neutrons

The effective dose of combined spectrum energy neutrons and high energy spectrum γ-rays in A-bomb survivors in Hiroshima and Nagasaki has long been a matter of discussion. The reason is largely due to the paucity of biological data for high energy photons, particularly for those with an energy of tens of MeV. To circumvent this problem, a mathematical formalism was developed for the photon energy dependency of chromosomal effectiveness by reviewing a large number of data sets published in the literature on dicentric chromosome formation in human lymphocytes. The chromosomal effectiveness was expressed by a simple multiparametric function of photon energy, which made it possible to estimate the effective dose of spectrum energy photons and differential evaluation in the field of mixed neutron and γ-ray exposure with an internal reference radiation. The effective dose of reactor-produced spectrum energy neutrons was insensitive to the fine structure of the energy distribution and was accessible by a generalized formula applicable to the A-bomb neutrons. Energy spectra of all sources of A-bomb γ-rays at different tissue depths were simulated by a Monte Carlo calculation applied on an ICRU sphere. Using kerma-weighted chromosomal effectiveness of A-bomb spectrum energy photons, the effective dose of A-bomb neutrons was determined, where the relative biological effectiveness (RBE) of neutrons was expressed by a dose-dependent variable RBE, RBE(γ, D _n), against A-bomb γ-rays as an internal reference radiation. When the newly estimated variable RBE(γ, D _n) was applied to the chromosome data of A-bomb survivors in Hiroshima and Nagasaki, the city difference was completely eliminated. The revised effective dose was about 35% larger in Hiroshima, 19% larger in Nagasaki and 26% larger for the combined cohort compared with that based on a constant RBE of 10. Since the differences are significantly large, the proposed effective dose might have an impact on the magnitude of the risk estimates deduced from the A-bomb survivor cohort.     

Protostrongylus rufescens: a cytogenetic study

The diploid chromosome number of Protostrongylus rufescens is 2n = 11 for males and 2n = 12 for females. So, the sex determinism mechanism is XO/XX. The study of the genetic behaviour of this species has been made. In diakinesis stage the bivalents show typical tetrads with cross, phi, and lineal configurations. The division of the sexual chromosome is prereductional for the first meiotic division.     

Stable chromosome aberrations in atomic bomb survivors: results from 25 years of investigation

Frequencies of stable chromosome aberrations from more than 3,000 atomic bomb survivors were used to examine the nature of the radiation dose response. The end point was the proportion of cells with at least one translocation or inversion detected in Giemsa-stained cultures of approximately 100 lymphocytes per person. The statistical methods allow for both imprecision of individual dose estimates and extra-binomial variation. A highly significant and nonlinear dose response was seen. The shape of the dose response was concave upward for doses below 1.5 Sv but exhibited some leveling off at higher doses. This curvature was similar for the two cities, with a crossover dose (i.e. the ratio of the linear coefficient to the quadratic coefficient) of 1.7 Sv (95% CI 0.9, 4). The low-dose slopes for the two cities differed significantly: 6.6% per Sv (95% CI 5.5, 8.4) in Hiroshima and 3.7% (95% CI 2.6, 4.9) in Nagasaki. This difference was reduced considerably, but not eliminated, when the comparison was limited to people who were exposed in houses or tenements. Nagasaki survivors exposed in factories, as well as people in either city who were outside with little or no shielding, had a lower dose response than those exposed in houses. This suggests that doses for Nagasaki factory worker survivors may be overestimated by the DS86, apparently by about 60%. Even though factory workers constitute about 20% of Nagasaki survivors with dose estimates in the range of 0.5 to 2 Sv, calculations indicate that the dosimetry problems for these people have little impact on cancer risk estimates for Nagasaki.     

HIV antibody assay that gave false negative results: multicentre collaborative study.

OBJECTIVE: To identify false negative results arising from the use of a commercial kit to detect antibody to HIV-1 and HIV-2 between July 1995 and March 1996. DESIGN: The 56 laboratories in the United Kingdom that were using the assay were asked to retrieve and retest specimens with an alternative assay for HIV-1 and HIV-2. Details of false negative results were obtained and these serum samples further investigated. SUBJECTS: 24,181 patients tested with the assay who were reported as being negative for HIV antibody. An additional 497 patients were confirmed as HIV positive with the assay. RESULTS: Serum samples of 20,973 of the patients were retested, and four patients were found to have had false negative results with the kit; three further patients were found to have had false negative results in the course of other laboratory testing. The seven patients with false negative results with the kit were of diverse risk group and HIV-1 subtype. Four had evidence of recent HIV infection. CONCLUSION: The commercial kit had a sensitivity of 99.2% (497/501), or less if the additional three patients with false negative results were taken into account.     

Chromosome numbers in representative myxomycetes: a cytogenetic study

Myxomycetes are also called plasmodial slime molds, due to one of their characteristic features, the occurrence of the plasmodium. However, most of the distinguishing characters of the five orders currently recognised are based on the morphology of fruiting bodies and spores. Although a few myxomycetes have become widely used model organisms for genetic and cytological studies, complete information relating to the number of chromosomes in haploid cells (n) is lacking thus far. Only two species of the order Physarales have been examined with respect to chromosome numbers. Here, we present a complete data set on the numbers of chromosomes in ten species of myxomycetes that are members of all five orders. Our analysis indicates that n?=?21 is the evolutionary ancient chromosome number that occurs in the morphologically simple orders Liceales and Ceratiomyxales. More derived taxa, such as the Physarales, have significantly higher chromosome numbers (n?=?30). These data shed light on the phylogenetic relationships within the myxomycetes.     

Biological control: lessons from a study of California red scale

A 20-year study of suppression of California red scale, a world-wide pest of citrus, by the parasitoid Aphytis melinus has established that the interaction is dynamically stable and that the mechanisms leading to control and stability operate at a local scale: spatial processes are not important. Key features appear to be an invulnerable class in the pest and rapid development of the parasitoid compared with the pest, as well as the fact that the parasitoid is an in situ specialist on the pest. Although another parasitoid species and two predator species are also present, they play at most a negligible role in pest control. These features—long-term persistence, suppression by a single natural enemy, an invulnerable stage in the pest and rapid development in the natural enemy—appear to be common in other coccid pest systems. By contrast, in temporary crops where the pest and enemy populations are open (i.e., sustained over the long run mainly by immigration) and non-persistent locally, as is frequently found in aphid pests, we expect that multiple generalist enemies are required for control and, of course, that spatial processes are important. There are very few well-studied examples of such systems, but these support our expectations. In these cases, it also appears that neither rapid enemy development nor an invulnerable pest stage is important for successful control.     

Structure and energy landscape of a photoswitchable peptide: a replica exchange molecular dynamics study

A replica exchange molecular dynamics (REMD) simulation of a bicyclic azobenzene peptide in explicit dimethyl sulfoxide solution is presented in order to characterize the conformational structures and energy landscape of a photoswitchable peptide. It is shown that an enhanced-sampling technique such as the REMD method is essential to obtain a converged conformational sampling of the peptide at room temperature. This is because conventional MD simulations of less than approximately 100-ns length are either trapped in local minima (at 295 K) or-if run at high temperature-do not resemble the room-temperature REMD results. Calculating various nuclear Overhauser effects (NOEs) and (3)J-couplings, a good overall agreement between the REMD simulations and the NMR experiments of Renner et al. (Biopolymers 2000;54:501-514) is found. In particular, the REMD study confirms the general picture drawn by Renner et al. that the trans-isomer of the azobenzene peptide exhibits a well-defined structure, while the cis-isomer is a conformational heterogeneous system; that is, the trans-isomer occurs in 2 well-defined conformers, while the cis-isomer represents an energetically frustrated system that leads to an ensemble of conformational structures. Employing a principal component analysis of the REMD data, the free energy landscape of the systems is studied at various temperatures. The implications for the folding and unfolding pathways of the system are discussed.     

Cytogenetic results of amniocentesis materials: incidence of abnormal karyotypes in the Turkish collaborative study

The experience on prenatal chromosome diagnosis of four Turkish centers participating in a collaborative study on 6041 genetic amniocentesis performed during a 4-8 years period were reviewed. 5887 (97.5%) patients had strong clinical indications for prenatal chromosome studies and 154 (2.5%) were referred because of maternal anxiety and a bad history of previous gestations. The main indication groups were: advanced maternal age (3197 cases), positive serum screening (2011 cases), ultrasound-identified anomaly (492 cases), previous fetus/child with chromosomal aberrations (103 cases), a history of a previous abnormal and/or mentally handicapped child (70 cases) and a parental chromosome rearrangement (14 cases). The average maternal age was 33.9 years and average gestational age was 18 weeks. A total of 179 affected fetuses were detected in this collaborative study (3%) of which 133 were unbalanced (74.3%). Among the 124 (69%) numerical aberrations, 102 (82.3%) were autosomal aneuploidies, 20 (16.1%) were gonosomal aneuploidies and 2 (1.6%) were poliploidies. Among the 55 (31%) structural aberrations, balanced translocation was the most common (63.6%) and 11 cases of inversion, four cases of unbalanced translocation, two cases of marker chromosome and three cases of other abnormalities were found. The overall culture success rate was 99.7%. Pregnancy termination that is permitted by legal authorities was accepted by 94.7% (126/133) with parents at unbalanced cytogenetic result announcement.     

Neutron-induced 63Ni in copper samples from Hiroshima and Nagasaki: a comprehensive presentation of results obtained at the Munich Maier-Leibnitz Laboratory

Those inhabitants of Hiroshima and Nagasaki who were affected by the A-bomb explosions, were exposed to a mixed neutron and gamma radiation field. Few years later about 120,000 survivors of both cities were selected, and since then radiation-induced late effects such as leukemia and solid tumors are being investigated in this cohort. When the present study was initiated, the fast neutron fluences that caused the neutron doses of these survivors had never been determined experimentally. In principle, this would have been possible if radioisotopes produced by fast neutrons from the A-bomb explosions had been detected in samples from Hiroshima and Nagasaki at distances where the inhabitants survived. However, no suitable radioisotope had so far been identified. As a contribution to a large international effort to re-evaluate the A-bomb dosimetry, the concentration of the radionuclide (63)Ni (half-life 100.1 years) has been measured in copper samples from Hiroshima and Nagasaki. These measurements were mainly performed at the Maier-Leibnitz-Laboratory in Munich, Germany, by means of accelerator mass spectrometry. Because the (63)Ni had been produced in these samples by fast A-bomb neutrons via the reaction (63)Cu(n,p)(63)Ni, these measurements allow direct experimental validation of calculated neutron doses to the members of the LSS cohort, for the first time. The results of these efforts have already been published in a compact form. A more detailed discussion of the methodical aspects of these measurements and their results are given in the present paper. Eight copper samples that had been significantly exposed to fast neutrons from the Hiroshima A-bomb explosion were investigated. In general, measured (63)Ni concentrations decreased in these samples with increasing distance to the hypocenter, from 4 x 10(6 ) (63)Ni nuclei per gram copper at 391 m, to about 1 x 10(5 ) (63)Ni nuclei per gram copper at about 1,400 m. Additional measurements performed on three large-distant copper samples from Hiroshima (distance to the hypocenter 1,880-7,500 m) and on three large-distant copper samples from Nagasaki (distance to the hypocenter 3,931-4,428 m) that were not exposed significantly to A-bomb neutrons, suggest a typical background concentration of about 8 x 10(4 ) (63)Ni nuclei per gram copper. If the observed background is accounted for, the results are consistent with state-of-the-art neutron transport calculations for Hiroshima, in particular for those distances where the victims survived and were included in the life span study cohort.