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PubMed1990

A generalized state-vector model for radiation-induced cellular transformation.

A mathematical model is developed, detailing the manner in which radiation brings about the transformation of cells to a state of uncontrolled growth. The model is based on the concepts of initiation and promotion, with the irradiation acting both to damage intracellular structures and to change the state of cells surrounding a damaged (initiated) cell. The complete model requires that the radiation produce two forms of damage within a cell, with at least one of the forms requiring an interaction which is a function of time since irradiation. Some form of contact inhibition must be removed, with this step being a function of the probability that a cell in an initiated state will be surrounded by n dead cells. The cell then must divide, with the probability of moving the cell to the final transformed state being a function of the number of cellular divisions. Prior to irradiation, it is assumed that cells may be characterized by an initial state vector describing the probability that any given cell is in one of the states specified by the model. The resulting model then is used to explain data concerning in vitro irradiation of cells by acute doses of X-rays, alpha particles and neutrons. Limited tests of the theory under conditions of fractionated irradiation are also provided. A controlling factor in such studies is the number of cells already in intermediate states prior to the irradiation.

Alpha Particles↗
PubMed1997

Lung cancer response following inhaled radon in the A/J and C57BL/6J mouse.

A/J and C57BL/6J mice, strains which differ in susceptibility to chemical-induced lung tumours, were examined for differential sensitivity to radon-induced lung cancer. Sixty weeks after exposure to 952 WLM radon (3.34 J h1 m-3), no lung tumours were found in the control, sham- (one dust-) exposed, or radon-exposed C57BL/6J mice. In contrast, each of the A/J groups had a substantial number of tumours. Although there were no differences in overall lung tumour incidence or multiplicity associated with radon and ore dust exposure in A/J mice, distinct differences in tumour size and histopathological appearance were noted. The ratio of lung adenoma-to-carcinoma found in control A/J mice was 10:1, whereas the ratio in one dust-exposed animals was 10:8 and that in radon-exposed animals was 8:6. Based on these data, particulates appear to modify the promotion-progression of lung cancer in this strain. In addition, the appearance of two very large carcinomas histologically resembling Clara-cell-derived tumours only in the radon-exposed A/J mice and the possibility of alpha-particle-induced killing of target cells in the radon-exposed animals suggests that A/J but not the C57BL/6J, mice may have genes that modify susceptibility to radon-induced lung cancer.

Alpha Particles↗
PubMed1978

[Production of 61Cu, 62Zn by alpha and 3He particle bombardment of natural nickel (author's transl)].

The optimum irradiation conditions were investigated for the production of 61Cu and 62Zn by alpha and 3He particle bombardment of natural nickel. Formation cross sections and thick-target yields were obtained for reaction products in the energy range of 10 to 40 MeV. For the production of 61Cu and 62Zn, the alpha particle bombardment was found superior to the 3He particle bombardment in so far as the yield was concerned. When the incident alpha energy of 21 MeV was chosen, after 2.4 hours of cooling, 2.1 mCi/muA.h of 61Cu could be produced with less than 1% of 60Cu contamination. For the production of 62Zn, when the incident alpha energy of 35 MeV and the target thickness of 57 mg /cm2 were chosen, 97.5 muCi/muA.h of 62Zn could be produced. Radiochemical purity of 62Zn was the highest at 12 hours after the end of bombardment.

Alpha Particles↗
PubMed1980

The value of the photoreactivable component in E. coli Bs-1 cells exposed to densely and sparsely ionizing radiations.

The dependence of the photoreactivation effect in E. coli Bs-1 cells on LET and energy of sparsely ionizing radiation was studied. The photoreactivation was shown to be absent after densely ionizing radiation (alpha-particles of 239Pu; fast neutrons En = 0.85 MeV) and after sparsely ionizing radiation with energies below 200 keV. In those cases where photoreactivation took place, the photoreactivable sector was found to increase with the voltage of the radiation.

Alpha Particles↗
PubMed2006

Standardization of 222Rn by LSC and comparison with alpha- and gamma-spectrometry.

Liquid scintillation counting (LSC) was used for the measurement of 222Rn in equilibrium with its daughters, with detection efficiency close to 5. The appropriate corrections were considered, including one related to the probability that the 165-micros half-life 214Po decays during the dead time of the counter initiated by the disintegration of his parent nuclide, 214Bi. The dead-time determination of a commercial LS counter is also presented using a 222Rn standard source. The LSC 222Rn sources were prepared by transfer of 222Rn produced by a solid 226Ra source into LSC cocktail frozen at 77K, flame-sealed afterwards. They were measured using the LNHB triple coincidence counter with adjustable extending-type dead-time unit, between 8 and 100 micros; two different procedures were used to calculate an effective dead time and then to deduce the counting rate extrapolated to zero dead-time value. The LSC results were compared with those obtained by cryogenic alpha-particle spectrometry (LNHB system) and by gamma-ray spectrometry for the same radon source in the LSC vial; the geometry transfer coefficient was calculated using the ETNA software. Measurement results and uncertainties are discussed.

Algorithms↗
PubMed1992

Radon: current challenges in cellular radiobiology.

Radon is by far the most important contributor to the collective dose equivalent. Most of what is known about the hazards of radon daughters comes from epidemiological studies of miners. There are a few well defined areas in which in vitro research can complement such studies: First, more data on the relative effects of differing energy (LET) alpha-particles would help: (1) understand the significance of the depth of sensitive cells in the bronchial epithelium--which varies between individuals, as well as between smokers and non-smokers, and between miners and non-miners; (2) understand the relative hazards of radon and thoron daughters. Second, reliable methods for predicting high LET responses from low LET response, would enable Japanese A-bomb survivor data to be applied with confidence. Third, understanding the effects of single-particle traversals of cells relative to multiple traversals could allow reliable extrapolation of epidemiological miner data to low exposures. Fourth, a better understanding of the nature of the interaction between tobacco and radiation damage would help predict the effect of radon on non-smokers.

Alpha Particles↗
PubMed1999

Lethality of single-track events: comparison between calculations and experimental data.

Recent results on cell killing by microbeams were analysed using three parameters (k, L, L1), where k is the mean number of lethal particles per cell nucleus, L [keV/microm] is the track-average LET (linear energy transfer) in cells, and L1 [keV/microm] is a critical value for inducing lethal damage by a single track. Analysis showed that calculations are consistent with two data sets. The existence of a quadratic dependence on LET of cellular effects is confirmed in the high-LET region between 30 and 500 keV/microm. L1 approximately 150 keV/microm was found to give the best fit and the sensitive area of the cell nucleus was determined as approximately 50 microm2 for Chinese hamster V79 cells. In microbeam experiments with several MeV alpha-particles, the relationship between k and L for V79 cells can be expressed as L = approximately 150(k)-1/2. For a given survival level, the difference in the required dose (or L) between the microbeam and broad-beam experiments is also analytically described.

Alpha Particles↗
PubMed2001

Monte Carlo track structure for radiation biology and space applications.

Over the past two decades event by event Monte Carlo track structure codes have increasingly been used for biophysical modelling and radiotherapy. Advent of these codes has helped to shed light on many aspects of microdosimetry and mechanism of damage by ionising radiation in the cell. These codes have continuously been modified to include new improved cross sections and computational techniques. This paper provides a summary of input data for ionizations, excitations and elastic scattering cross sections for event by event Monte Carlo track structure simulations for electrons and ions in the form of parametric equations, which makes it easy to reproduce the data. Stopping power and radial distribution of dose are presented for ions and compared with experimental data. A model is described for simulation of full slowing down of proton tracks in water in the range 1 keV to 1 MeV. Modelling and calculations are presented for the response of a TEPC proportional counter irradiated with 5 MeV alpha-particles. Distributions are presented for the wall and wall-less counters. Data shows contribution of indirect effects to the lineal energy distribution for the wall counters responses even at such a low ion energy.

Algorithms↗
PubMedDate not supplied

Neutron flux-density and secondary-particle energy spectra at the 184-inch synchrocyclotron medical facility.

We have identified the sources of neutron production in the beam transport system of the 720-MeV helium beam used for radiation therapy at the 184-in synchrocyclotron of the Lawrence Berkeley Laboratory, and determined their magnitude. Measurements with activation detectors of differing energy response were used to unfold secondary particle spectra at various locations on the patient table. The effect of charged particles was estimated using a calculation of neutron-flux densities derived from published cross sections. The absorbed dose, as a function of distance from the beam axis, was calculated using the unfolded spectra and evaluated fluence-to-dose conversion factors. The values of absorbed dose obtained from the unfolding of experimental data agree with the values obtained from the calculated spectra within the estimated uncertainty of +/- 25%. These values are approximately 5 X 10(-3) rad on the beam axis and approximately 1 X 10(-3) rad at distances greater than 20 cm, perpendicular to the beam axis, per rad deposited by the incident alpha-particle beam in the plateau. Estimates of upper limits of dose to two critical organs, the lens of the eye and red bone marrow, are approximately 25 rad and approximately 5 rad, respectively, for a typical treatment plan.

Alpha Particles↗
PubMed2005

Some more new etchants for CR-39 detector.

Recently, several new etchants have been reported for CR-39 detector (Molten Ba(OH)2. 8H2O as an etchant for CR-39 detector, Radiat. Meas. 37 (2003) 205; Discovery of new etchants for CR-39 detector, Radiat. Meas. (2004)). We have made further progress in this direction and have unveiled two more new etchants which are reported in this article. CR-39 detectors were irradiated with fission fragments and alpha particles from a thin 252Cf disc source. The irradiated detectors were then etched in our newly introduced etching solutions as well as in conventionally used 6 M NaOH aqueous solution at 70 degrees C. The newly prepared etching solutions included NaOH dissolved in methanol and NaOH dissolved in methanol + water. Optimum values of NaOH concentration in methanol as well as in methanol + water were determined. Optimum etching temperatures were also determined for both the above-mentioned etchants. From fission and alpha track diameters, bulk etching rate (VB), track etching rate (VT) and etching efficiency (eta) were determined and compared with that obtained for 6 M NaOH at 70 degrees C. Both the newly introduced etchants were found more efficient than the conventionally used 6 M aqueous NaOH (64%) at 70 degrees C and have relatively much smaller etching time.

Alpha Particles↗
PubMed1994

RBE: mechanisms inferred from cytogenetics.

Cyclotron-accelerated heavy ion beams provide a fine degree of control over the physical parameters of radiation. Cytogenetics affords a view into the irradiated cell at the resolution of chromosomes. Combined they form a powerful means to probe the mechanisms of RBE. Cytogenetic studies with high energy heavy ion beams reveal three LET-dependent trends for 1) level of initial damage, 2) distribution of damage among cells, and 3) lesion severity. The number of initial breaks per unit dose increases from a low-LET plateau to a peak at approximately 180 keV/micrometer and declines thereafter. Overdispersion of breaks is significant above approximately 100 keV/micrometer. Lesion severity, indicated by the level of chromosomal fragments that have not restituted even after long repair times, increases with LET. Similar studies with very low energy 238Pu alpha particles (120 keV/micrometer) reveal higher levels of initial breakage per unit dose, fewer residual fragments and a higher level of misrepair when compared to high energy heavy ions at the same LET. These observations would suggest that track structure is an important factor in genetic damage in addition to LET.

Alpha Particles↗
PubMed2002

Track structure for low energy ions including charge exchange processes.

The model and development is described of a new generation of Monte Carlo track structure codes. The code LEPHIST simulates full slowing down of low-energy proton history tracks in the range 1 keV-1 MeV and the code LEAHIST simulates low-energy alpha particle history tracks in the range 1 keV-8 MeV in water. All primary ion interactions are followed down to 1 keV and all electrons to 1 eV. Tracks of secondary electrons ejected by ions were traced using the electron code KURBUC. Microdosimetric parameters derived by analysis of generated tracks are presented.

Alpha Particles↗
PubMed2000

Model for radial dependence of frequency distributions for energy imparted in nanometer volumes from HZE particles.

This paper develops a deterministic model of frequency distributions for energy imparted (total energy deposition) in small volumes similar to DNA molecules from high-energy ions of interest for space radiation protection and cancer therapy. Frequency distributions for energy imparted are useful for considering radiation quality and for modeling biological damage produced by ionizing radiation. For high-energy ions, secondary electron (delta-ray) tracks originating from a primary ion track make dominant contributions to energy deposition events in small volumes. Our method uses the distribution of electrons produced about an ion's path and incorporates results from Monte Carlo simulation of electron tracks to predict frequency distributions for ions, including their dependence on radial distance. The contribution from primary ion events is treated using an impact parameter formalism of spatially restricted linear energy transfer (LET) and energy-transfer straggling. We validate our model by comparing it directly to results from Monte Carlo simulations for proton and alpha-particle tracks. We show for the first time frequency distributions of energy imparted in DNA structures by several high-energy ions such as cosmic-ray iron ions. Our comparison with results from Monte Carlo simulations at low energies indicates the accuracy of the method.

Alpha Particles↗
PubMed1998

Radiation-induced transmissable chromosomal instability in haemopoietic stem cells.

Heritable radiation-induced genetic alterations have long been assumed to be "fixed" within the first cell division. However, there is a growing body of evidence that a considerable fraction of cells surviving radiation exposure appear normal, but a variety of mutational changes arise in their progeny due to a transmissible genomic instability. In our investigations of G-banded metaphases, non-clonal cytogenetic aberrations, predominantly chromatid-type aberrations, have been observed in the clonal descendants of murine and human haemopoietic stem cells surviving low doses (approximately l track per cell) of alpha-particle irradiations. The data are consistent with a transmissible genetic instability induced in a stem cell resulting in a diversity of chromosomal aberrations in its clonal progeny many cell divisions later. Recent studies have demonstrated that the instability phenotype persists in vivo and that the expression of chromosomal instability has a strong dependence on the genetic characteristics of the irradiated cell. At the time when cytogenetic aberrations are detected, an increased incidence of hprt mutations and apoptotic cells have been observed in the clonal descendants of (alpha-irradiated murine haemopoietic stem cells. Thus, delayed chromosomal abnormalities, delayed cell death by apoptosis and late-arising specific gene mutations may reflect diverse consequences of radiation-induced genomic instability. The relationship, if any, between these effects is not established. Current studies suggest that expression of these delayed heritable effects is determined by the type of radiation exposure, type of cell and a variety of genetic factors.

Alpha Particles↗
PubMed2006

High-linear energy transfer irradiation targeted to skeletal metastases by the alpha-emitter 223Ra: adjuvant or alternative to conventional modalities?

The bone-seeking, alpha-particle-emitting radiopharmaceutical Alpharadin, 223RaCl2 (half-life=11.4 days), is under clinical development as a novel treatment for skeletal metastases from breast and prostate cancer. This article summarizes the current status of preclinical and clinical research on 223RaCl2. Potential advantages of 223Ra to that of external beam irradiation and registered beta-emitting bone seekers are discussed. Published data of 223Ra dosimetry in mice and a therapeutic study in a skeletal metastases model in nude rats have indicated significant therapeutic potential of bone-seeking alpha-emitters. This article provides short-term and long-term results from the first clinical single dosage trial. We also present data from a repeated dosage study of five consecutive injections of 50 kBq/kg body weight, once every 3rd week, or two injections of 125 kBq/kg body weight, 6 weeks apart. Furthermore, interim results are described for a randomized phase 2 trial involving 64 patients with hormone-refractory prostate cancer and painful skeletal metastases who received four monthly injections of 223Ra or saline as an adjuvant to external beam radiotherapy. Lastly, we present preliminary dose estimates for 223Ra in humans. Results indicate that repeated dosing is feasible and toxicity is low, and that opportunities are available for combined treatment strategies.

Alpha Particles↗
PubMed1979

Effect of elevated temperatures on the radiation sensitivity of yeast cells of different species.

The influence of hyperthermia on the survival of irradiated yeast cells of different species has been studied. The experiments reported in the paper have shown: (1) simultaneous action of ionizing radiation and high temperatures appeared to increase the radiation response by a factor of approximately 2.7 for diploid and only by a factor of 1.5 for haploid cells of wild-type; (2) the combined action of high temperature and ionizing radiation had no synergistic effect for rad51 mutant diploid yeast cells; (3) heating before or after irradiation did not alter the radiation response of yeast cells; (4) enhancement of yeast cell sensitivity by simultaneous action of hyperthermia and 239Pu-alpha-particles was negligible; (5) the magnitude and the rate of liquid holding recovery is lowered with increasing of irradiation temperature. On this basis, it was concluded that possible mechanism for thermal sensitization of yeast cells may involve the reduced capacity of cells to recover damages resulted from the combined action of both modalities.

Alpha Particles↗
PubMed2002

Investigation of radiation damage in DNA by using atomic force microscopy.

The effect of radiations on supercoiled plasmid DNA has been investigated by using atomic force microscopy (AFM). The DNA molecules were deposited on a substrate and observed by AFM. Alternatively, DNA at different scavenger concentrations was initially exposed to different types of radiations (alpha and X rays) at various doses. After irradiation, fragments (open circular and linearised strands) were observed corresponding to single strand breaks and double strand breaks in DNA. This result indicates the capabilities of AFM for the qualitative detection of strand modifications due to irradiation. The amount of each class of topology enables a quantitative response to be determined for both types of radiation (alpha, X). A value of the radiosensitivity of DNA was obtained as a function of the scavenger concentration. Strong accordance was found between AFM results and those obtained by use of gel electrophoresis. The advantage of AFM in comparison with traditional techniques is the possibility of analysing the radiation effects on one molecule. Indeed, taking the example of alpha particles, it is shown that it is easy to measure the sizes of linear strands by AFM. Such additional or even precise results are difficult to obtain with gel electrophoresis since, in such a case, data are lost through smearing.

Alpha Particles↗