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Biomedical subjects

J Booz

Publications and source records attributed to J Booz.

At least 19 recordsLinked to original sources
PubMed1995

Cellular mechanisms of protection and repair induced by radiation exposure and their consequences for cell system responses.

The complex biological systems that constitute living organisms operate at various levels of organization, from the atomic-molecular to the cellular to the organ-organism level. The response of an organism to disturbances that are detrimental to structure and function generally begin at the level of organization where the primary injury has occurred. Detriment that occurs from simultaneous or sequential, or single or multiple interactions at a relatively low level of organization tends to be transferred to higher levels. However, at each level of organization there is a given probability of such detriment being removed according to the tolerance to injury that is peculiar to that level. There is thus a direct relationship between the frequency of injurious events at a lower level of organization, and the degree of structural complexity of the system at the high level at which such detriment is eventually manifested. The extent of structural disruption at any given level determines the degree of functional failure at that level. In the exposure of tissue to ionization radiation, the primary injury begins with energy deposition events (tracks or hits) consisting of many ionizations and excitations in localized clusters of submicroscopic dimensions at the atomic-molecular level of organization within the cell, and the cell is affected as a whole. The cell is the elementary unit of life and the sum of the individual cell responses determines the response of the tissue and the organism. Individual cell responses are nevertheless found to differ in type and degree depending on the absorbed dose. With decreasing values of absorbed dose to the tissue, the probability of a cell being hit by an energy deposition event decreases linearly. At very low values of absorbed dose to tissue, only a fraction of the total cell population experiences single hits and these are of different sizes. The size distribution or spectrum of these hits is invariant, independent of their total number over a considerable range at low-dose levels and is determined only by the type and quality of the given radiation. The probability that a hit cell will suffer a given detriment such as a chromosomal aberration, gene mutation or death has been shown to increase in a sigmoid fashion with increasing hit size.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Energy deposition by protons and alpha particles in spherical sites of nanometer to micrometer diameter.

Monte Carlo stimulated proton- and alpha-particle tracks in water vapor were used to develop an analytical function for calculating number distributions of ionizations induced in spherical sites. For charged particles crossing the site, Fermi-like functions were used to approximate the ionization distributions. Ionization event distributions due to particles passing outside the site were approximated with an exponentially decreasing function. The function parameters were calculated for protons and alpha particles in the energy range 0.3-5.0 MeV/amu and for site diameters of 1 to 1000 nm. The quality of fit obtained is very good for the particles, energy range and site diameters considered.

Alpha Particles↗
PubMed1988

What is a 'low dose' of radiation?

Although the expression of radiation-induced biological effects and responses may be at either the cell, organ or organism level, induction of some of these phenomena (e.g. cancer of clastogenic and genetic effects) can have their origin in the interaction of a single charged particle with the target-containing volume (TCV) of the cell, e.g. the cell nucleus. However, the independent variable now used in both organ and cell population studies, the absorbed dose to the organ, provides no information directly on particle-TCV interactions. Even if calculated as a mean to an organized population of cells, the absorbed dose becomes a composite and confounded quantity, (FzN), in which F is the fraction of TCVs 'hit' by a particle during a given exposure, z is the mean value of z1, the energy absorbed in the TCV in a single hit, and N is the mean number of hits per affected TCV. Scientific precepts demand the avoidance of such confounded variables by achieving their isolation. The needed separation can be effected by the use of microdosimetric techniques, which make it possible to hold one component quantity constant while the others are varied. As an example, low-level radiation exposure (LLE) can be used to hold F at a constant value of 0.2 where, on average, there is but one hit per TCV. The probability of a cellular quantal response, as a function of z1 only, can then be determined by use of LLE to radiations covering a wide span of LETs. Conversely, the effect of varying only the fraction of cells hit can be studied by holding z constant. This can be accomplished by working within a narrow band of LET, but only in the LLE range. The effectiveness of preirradiation altering cell sensitivity as a function of the number of hits per TCV can be determined by working within, and somewhat above, the LLE range. In either risk assessment or the application of radiation as a pretreatment, minimal consequences can be assured only if very low-level exposure is employed in order that F will be small, and if the exposure is in a field of radiation of very low LET so that z1 will be as small as possible. That is to say, exposure conditions with low consequences cannot be specified in terms of any single quantity.

Dose-Response Relationship, Radiation↗
PubMed1988

A microdosimetric understanding of low-dose radiation effects.

This paper presents a microdosimetric approach to the problem of radiation response by which effects produced at low doses and dose rates can be understood as the consequences of radiation absorption events in the nucleus of a single relevant cell and in its DNA. Radiation absorption at the cellular level, i.e. in the cell nucleus as a whole, is believed to act through radicals. This kind of action is called 'non-specific' and leads to the definition of an 'elemental dose' and the 'integral response probability' of a cell population. Radiation absorption at the molecular level, i.e. in sensitive parts of the DNA, is thought to act through double-strand breaks. This kind of action is called 'specific' and leads to a 'relative local efficiency'. In general, both mechanisms occur for all types of radiation; however, it is the dose contribution of both specific and non-specific effects that determines the radiation quality of a given radiation. The implications of this approach for the specification of low-dose and low dose-rate regions are discussed.

Cells↗
PubMed1988

Biochemical and cellular mechanisms of low-dose effects.

Low-dose irradiation is usually considered to be rather ineffective in producing biologically relevant effects. Yet, individual radiation absorption events within cell nuclei or whole cells interact stochastically with subcellular structures due to the multiple ionizations along primary or secondary particle tracks, depending on ionization density. Whereas radiation effects are usually seen in the context of structure and function of DNA, other cellular effects, perhaps influencing DNA by secondary biochemical mechanisms, also warrant attention. Thus, previous work from this laboratory with bone marrow that was obtained from whole-body exposed mice, has shown that single or few instantaneous radiation absorption events per cell from gamma-rays produce an acute and temporary partial inhibition of the enzyme thymidine kinase; the effect appears within about 1 h after the event, reaches its maximum at approximately 4 h and disappears completely within another 6 h. This pattern of enzyme inhibition is fully concordant with the pattern of inhibition of uptake of tritiated thymidine or 125I-labelled deoxyuridine into the DNA; also concordant is a temporary increase in the concentration of free thymidine in the blood serum of the exposed mice. The particular response of thymidine kinase was considered to relate to some, thus far unknown, repair systems and/or to a defence mechanism of the hit cells. In order to further elucidate the role of the acute and temporary partial inhibition of thymidine kinase in cellular metabolism, experiments were carried out in which mice were acutely exposed to 0.01 or 0.1 Gy and again exposed to the same dose at different times up to 12 h after the first exposure. At regular time intervals after the second exposure bone marrow cells were obtained and thymidine kinase activity was studied by various assays. The results indicate that the first acute irradiation conditioned the cells in such a way that the second acute irradiation produced either an enhanced inhibition and recovery of thymidine kinase activity, or no effect at all was seen, when the second irradiation was given between about 3 and 8 h after the first irradiation. From 8 to 12 h after the first irradiation the cells apparently resumed their original state, so that the second irradiation produced effects quite similar to those seen after a single irradiation in unconditioned cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Auger-electron cascades, charge potential and microdosimetry of iodine-125.

This paper is a contribution to the microdosimetry of I-125. It shows microdosimetric spectra of individual and average disintegrations of I-125 for various target sizes and gives evidence for the relative contributions of energy-deposition events of low and high LET. It further presents information on the relative efficiencies of Auger-electrons and multiple charges in terms of local energy deposition, e.g. to model targets of DNA, and discusses their radiobiological implications, e.g. the microdosimetric understanding of the different efficiencies of specific and random incorporations of I-125. When I-125 is specifically incorporated into DNA, most of the energy deposition events are very large, e.g. above 40 keV/micron for a simulated target volume of 20 nm diameter, regardless of the number and energy of Auger electrons emitted. Therefore it is not necessary, for the discussion of the radiobiological implications, to distinguish between different classes of disintegrations. For unspecific, homogeneous incorporation of I-125 somewhere into tissue, about 20% of the dose to critical targets of 25 nm diameter is made up by disintegrations that happen to occur within these targets. When assuming that other critical targets and target structures can be neglected, this part of the dose will be equally effective as in the case of specific incorporation of I-125 into such target models. In addition, there are the normal, low-LET radiation effects from the other, 80% large fraction of the dose. With this information, for the biological systems and end points for which a short section of the elemental chromatine fiber can be taken as the relevant critical target, it is shown that the expected D37 value for homogeneous unspecific incorporation of I-125 can be estimated when the D37 for specific incorporation in DNA is known. For an example calculation, the estimated D37-value for nonspecific, homogeneous incorporation of I-125 would be about half as effective as specifically incorporated I-125. Thus, the microdosimetric data of the present work show that a high efficiency of homogeneous incorporation of I-125 into the cell nucleus is not necessarily in contradiction with the idea of I-125 disintegrations inside the DNA being the main cause of radiation action.

DNA↗
PubMed1987

A microdosimetric interpretation of the radiobiological effectiveness of 125I and the problem of quality factor.

When considering the microdosimetric energy deposition in small biological targets the Auger electron emitter 125I behaves like a high-LET radiation. For a specific incorporation in sensitive biological volumes of 20 nm in diameter a mean lineal energy of gamma F approximately equal to 270 keV micron-1 has been evaluated. Experimental data on transformation, mutation and chromosome aberration from DNA-bound 125I are interpreted to yield RBE-values, relative to 200 kV X rays, of 32 to 38 (transformations), 1 to 16 (mutations) and 6 to 77 (chromosome aberrations). Thus the RBE for transformation and chromosome aberration tends to be larger than the ICRP recommended high-LET quality factor (Q = 20). The implications of these results for the function Q(L) applied in radiation protection will be discussed.

Animals↗
PubMed1987

A Monte Carlo simulation of Auger cascades.

The energy imparted to biological tissue after the decay of incorporated Auger emitters stems from two sources: (a) energy deposition by the Auger and Coster-Kronig electrons and (b) the charge potential which remains on the multiple ionized atom after the end of the cascade. For the numerical assessment of both the kinetic energy of the released electrons and the charge potential, a new and--for purposes of microdosimetry--precise method is presented. Based on relativistic Dirac-Fock calculations and a rigorous bookkeeping, this method provides a perfect energy balance of the considered atomic system when applied to Monte Carlo simulations of Auger cascades. By comparing the results for charge distribution for krypton and iodine with experimental data and the electron spectrum of 125I with theoretical data, it can be shown that the approach followed in this work is reasonable and appropriate for the determination of the energy deposited by incorporated Auger emitters in small volumes of condensed matter. The total energy deposited by 125I in a volume of 20-nm diameter is 2.03 keV which is made up by multiple ionization (1.07 keV) and energy deposition by the emitted Auger electrons (0.96 keV).

Chemical Phenomena↗
PubMed1987

Some consequences of the Auger effect: fluorescence yield, charge potential, and energy imparted.

The potential energy produced by the Auger cascade due to the charging of atoms is evaluated and incorporated into conventional treatment of energy deposition. A straightforward method for calculating this energy is presented. For the photoelectric interaction the potential energy is shown to be at least as important as L-shell fluorescence in calculating the electron kerma. For radioactive decay by electron capture or internal conversion, it is shown that, for small (less than 100 nm) targets containing the decay, the atomic charging can be the dominant contribution to the total energy deposited in the target.

Bromine↗
PubMed1985

Non-invasive investigations of the growth kinetics of a solid experimental tumor (sarcoma-180).

The investigations reported were performed to test applicability of non-invasive methods for the measurement of the parameters determining the growth of a solid experimental tumor and to measure these data for the tumor system sarcoma-180/NMRI-mice. It could be shown that non-invasive methods can be used for the measurement of tumor growth, especially the fraction of proliferating cells (growth fraction) which is of special importance for tumor therapy. For the tumor system under investigation, the growth is completely determined by an exponential decrease of the growth fraction.

Animals↗
PubMed1984

Development of dose equivalent meters based on microdosimetric principles.

In this paper, the employment of microdosimetric dose-equivalent meters in radiation protection is described considering the advantages of introducing microdosimetric methods into radiation protection, the technical suitability of such instruments for measuring dose equivalent, and finally technical requirements, constraints and solutions together with some examples of instruments and experimental results. The advantage of microdosimetric methods in radiation protection is illustrated with the evaluation of dose-mean quality factors in radiation fields of unknown composition and with the methods of evaluating neutron- and gamma-dose fractions. --It is shown that there is good correlation between dose-mean lineal energy, yD, and the ICRP quality factor. --Neutron- and gamma-dose fractions of unknown radiation fields can be evaluated with microdosimetric proportional counters without recurrence to other instruments and methods. The problems of separation are discussed. The technical suitability of microdosimetric instruments for measuring dose equivalent is discussed considering the energy response to neutrons and photons and the sensitivity in terms of dose-equivalent rate. Then, considering technical requirements, constraints, and solutions, the problems of the large dynamic range in LET, the large dynamic range in pulse rate, geometry of sensitive volume and electrodes, evaluation of dose-mean quality factors, calibration methods, and uncertainties are discussed.

Gamma Rays↗
PubMed1984

Acute and temporary inhibition of thymidine kinase in mouse bone marrow cells after low-dose exposure.

Low-dose whole-body exposure of mice to less than 0.01 Gy gamma-rays causes inhibition of incorporation of thymidine or 5-iodo-2-deoxyuridine into DNA of bone-marrow cells in vitro; the effect is maximal in cells at 4 hours after exposure and then subsides within about 10 hours. This is due to the inhibition of cellular thymidine kinase, which gradually develops to a maximum at 4 hours after exposure and again subsides within the next 10 hours. This inhibition involves only 35 per cent of the entire cellular enzyme activity and, analogous to the depression of thymidine incorporation into the cells, is only seen when the cells are collected into medium that is buffered to 7.2-7.4 and contains about 1350 mg NaHCO3 per litre. Addition of NaHCO3 to the cell homogenate or to the high speed supernatant containing the enzyme, but not to intact cells, failed to produce enzyme inhibition. There is also no depression of 5-iodo-2-deoxyuridine uptake into the intact cells in vitro when the mice are irradiated either shortly before or after i.v. injection of 0.02 mg of procain chloride. The reversibility of the effect in vivo and in vitro suggests a particular enzyme control mechanism that may be non-specifically triggered by intracellular charges, such as peroxides, and may enhance repair.

Animals↗
PubMed1982

Acute non-stochastic effect of very low dose whole-body exposure, a thymidine equivalent serum factor.

Whole-body irradiation of mice causes the dose-dependent appearance of a humoral factor in blood serum which inhibits incorporation of 125-IUdR into tissue culture cells. This factor appears even at doses below 0.01 Gy gamma irradiation and thus is probably not related to cell death. Data are presented relating this humoral factor to thymidine. Since at low doses the target size for this effect was calculated to be the entire cell, a cellular effect is postulated linking the site of few primary absorption events, anywhere in the cell, with the cellular membrane, thus causing changes in membrane charge, structure and/or fluidity. This may lead to blocking thymidine acceptance by the cell, and thus would cause a pile-up of thymidine in the reutilization pathway in peripheral blood and would give rise to the observed effect. The effect appears as a temporary disturbance of the physiological equilibrium and should not be related at present to any cellular damage. The acute low-dose effect described has implications for the measurement of low-dose exposure by biological dosimeters and on basic research on membrane function.

Animals↗
PubMed1981

Cellular and nuclear volume of human cells during the cell cycle.

The volumes of whole cells and nuclei of cultured human cells were studied at different times after synchronization of growth using the Coulter counter and scanning microphotometry. It was found that the increase in cell volume is compatible with both linear or exponential growth during the cell cycle. The growth of the nuclear volume is not correlated with the beginning of the DNA synthesis. The nuclear volume starts to increase already 6 hr prior DNA synthesis. The data also indicate that the nuclear volume growth could proceed in two stages. The relation of this result to radiation sensitivity is discussed.

Cell Cycle↗
PubMed1981

Low dose effect of ionizing radiation on incorporation of iododeoxyuridine into bone marrow cells.

The reduction of the incorporation of IUdR in bone marrow cells depends on the time after irradiation and on te microenvironment of the cells. The strongest effect is observed 4 hours after irradiation. For absorbed doses above 40 rad, whole-body irradiated mice were more sensitive with respect to depression of IUdR incorporation in bone marrow cells, when the bone marrow cells were labelled in vivo, and less sensitive for in vitro labelling. The converse was observed for very small doses of 1 rad and below. Such small doses resulted in a significant depression of IUdR incorporation after in vivo irradiation and in vitro labelling and showed no effect at all after in vivo irradiation and in vivo labelling. The least effect of radiation was observed after both irradiation and labelling in vitro. Although the mechanisms are not fully understood, the biological results and microdosimetric considerations indicate that at the smallest doses the effect is due to functional changes of cellular organelles which control intracellular mechanisms. A working hypothesis is proposed for the reduction of IUdR incorporation at low doses as being due to functional changes of the cellular membranes.

Animals↗
PubMed1981

Microdosimetric investigations on collimated fast-neutron beams for radiation therapy: I. Measurements of microdosimetric spectra and particle dose fractions in a water phantom for fast neutrons from 14 MeV deuterons on beryllium.

Lineal energy spectra of fast neutrons, produced by bombarding a thick beryllium target with 14 MeV deuterons, were measured with a proportional counter simulating a sensitive diamter of 2 micrometers. The mean neutron energy of the collimated beam was 6 MeV. The total lineal energy spectra, measured at different positions within a water phantom were separated into three different components: the gamma component, the recoil-proton component, and the component of heavier recoil ions. It is shown mathematically that the components of a linear energy spectrum thus derived allow the calculation of their fractional dose contributions. These dose fractions i.e. the gamma dose, the recoil-proton dose, and the dose fraction of heavier recoil ions, are shown as a function of the spatial position in the phantom.

Beryllium↗