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Lethal, potentially lethal lesion model

Description: A theoretical framework to describe the formation of lethal mutations by radiation is presented. Lesions that are repaired (and misrepaired) in each type of experiment described (delayed plating and split dose) are assumed to be the same. In this model the same (potentially lethal) lesions cause both sublethal and potentially lethal damage. Potentially lethal damage is defined as damage which may be modified by alterations in postirradiation conditions. Sublethal damage is cellular damage whose accumulation may lead to lethality. A crucial consideration in the expression of the damage is the kind of medium in which the cells are placed during the repair period. Fresh or growth medium (F-medium) is assumed to cause fixation of damage after about 3 hours, while no fixation (only misrepair) occurs in conditioned medium (C-medium).
Date: July 1, 1983
Creator: Curtis, S.B.
Partner: UNT Libraries Government Documents Department

New particles and their application in medicine

Description: In recent years there has been increasing interest in the use of new particle beams for various medical applications. The particles being used, fast neutrons, protons, helium ions, negative pions, and heavy ions, have in fact been known and studied for over forty years. They are new only in the sense that, until recently, the medical community has had little experience with them in the clinic. The applications of these new particles to clinical medicine, primarily in the areas of tumor radiotherapy and diagnostic radiography are reviewed.
Date: September 1, 1979
Creator: Curtis, S.B.
Partner: UNT Libraries Government Documents Department

Ideas on the unification of radiobilogical theories

Description: A unified formulation of cell inactivation has been developed that incorporates major ideas of several theories (hypotheses) of how individual mammalian cells are inactivated by ionizing radiation. Elements from the repair-misrepair, lethal-potentially lethal, sublesion interaction, and track structure models are combined to produce a single set of mutually compatible hypotheses.
Date: October 1, 1982
Creator: Curtis, S.B.
Partner: UNT Libraries Government Documents Department

Application of the LPL model to mixed radiations

Description: The LPL (Lethal, Potentially Lethal) formulation was used to analyze sets of cell survival data from mixes of (1) alpha particles and X rays and (2) neon ions and X rays. The hypothesis tested was whether survival after mixed radiation could be predicted by simply adding the total number of lethal and potentially lethal lesions from each radiation in the theoretical survival expression. Results show that all data appear to conform satisfactorily to the LPL hypothesis except for the mixed neon-ion and X-ray results with a large dose of X rays (8 Gy) given first. 8 refs., 6 figs., 1 tab.
Date: September 1, 1991
Creator: Curtis, S.B.
Partner: UNT Libraries Government Documents Department

Mechanistic models

Description: Several models and theories are reviewed that incorporate the idea of radiation-induced lesions (repairable and/or irreparable) that can be related to molecular lesions in the DNA molecule. Usually the DNA double-strand or chromatin break is suggested as the critical lesion. In the models, the shoulder on the low-LET survival curve is hypothesized as being due to one (or more) of the following three mechanisms: (1) interaction'' of lesions produced by statistically independent particle tracks; (2) nonlinear (i.e., linear-quadratic) increase in the yield of initial lesions, and (3) saturation of repair processes at high dose. Comparisons are made between the various approaches. Several significant advances in model development are discussed; in particular, a description of the matrix formulation of the Markov versions of the RMR and LPL models is given. The more advanced theories have incorporated statistical fluctuations in various aspects of the energy-loss and lesion-formation process. An important direction is the inclusion of physical and chemical processes into the formulations by incorporating relevant track structure theory (Monte Carlo track simulations) and chemical reactions of radiation-induced radicals. At the biological end, identification of repair genes and how they operate as well as a better understanding of how DNA misjoinings lead to lethal chromosome aberrations are needed for appropriate inclusion into the theories. More effort is necessary to model the complex end point of radiation-induced carcinogenesis.
Date: September 1, 1990
Creator: Curtis, S.B.
Partner: UNT Libraries Government Documents Department

Mechanistic models

Description: Several models and theories are reviewed that incorporate the idea of radiation-induced lesions (repairable and/or irreparable) that can be related to molecular lesions in the DNA molecule. Usually the DNA double-strand or chromatin break is suggested as the critical lesion. In the models, the shoulder on the low-LET survival curve is hypothesized as being due to one (or more) of the following three mechanisms: (1) ``interaction`` of lesions produced by statistically independent particle tracks; (2) nonlinear (i.e., linear-quadratic) increase in the yield of initial lesions, and (3) saturation of repair processes at high dose. Comparisons are made between the various approaches. Several significant advances in model development are discussed; in particular, a description of the matrix formulation of the Markov versions of the RMR and LPL models is given. The more advanced theories have incorporated statistical fluctuations in various aspects of the energy-loss and lesion-formation process. An important direction is the inclusion of physical and chemical processes into the formulations by incorporating relevant track structure theory (Monte Carlo track simulations) and chemical reactions of radiation-induced radicals. At the biological end, identification of repair genes and how they operate as well as a better understanding of how DNA misjoinings lead to lethal chromosome aberrations are needed for appropriate inclusion into the theories. More effort is necessary to model the complex end point of radiation-induced carcinogenesis.
Date: September 1, 1990
Creator: Curtis, S. B.
Partner: UNT Libraries Government Documents Department

Single track effects, biostack and risk assessment

Description: This talk addresses the single-track nature of the space radiation environment, and points out the importance of single hits'' in the evaluation of radiation risk for long-term missions occurring outside the earth's magnetic field. A short review is made of biological objects found to show increased effects when hit'' by a single heavy charged-particle in space. A brief discussion is given of the most provocative results from the bacterial spore B. subtilis: experimental evidence that tracks can affect biological systems at much larger distances from the trajectory than previously suspected, and that the resultant inactivation cross section in space calculated for this system is very large. When taken at face value, the implication of these results, when compared to those from experiments performed at ground-based accelerators with beams at low energies in the same LET range, is that high-energy particles can exert their influence a surprising distance from their trajectory and the inactivation cross sections are some twenty times larger than expected. Clearly, beams from high-energy heavy-ion accelerators should be used to confirm these results. For those end points that can also be caused by low-LET beams such as high-energy protons, it is important to measure their action cross sections as well. The ratio of the cross sections for a high-LET beam to that of a low-LET beam is an interesting experimental ratio and, we suggest, of more intrinsic interest than the RBE. It is a measure of the biological'' importance of one particle type relative to another particle type. This ratio will be introduced and given the name RPPE (Relative Per Particle Effectiveness). Values of RPPE will be discussed.
Date: October 1, 1992
Creator: Curtis, S.B.
Partner: UNT Libraries Government Documents Department

Wobbler facility for biomedical experiments at the Bevalac

Description: A new wobbler facility has been developed to deliver large uniform fields of relativistic heavy ions at the Bevalc without resorting to the use of scattering material in the beam. The charged particle beams are made to wobble and 'paint' a ring at the target by a pair of dipole magnets, which are placed tandem with their fields orthogonal to each other. The magnets are powered sinusoidally 90/sup 0/ out of phase with each other. By superimposing several rings of appropriate sizes and intensities, large uniform fields are produced. Up to 30 cm diameter fields with less than 5% variation in uniformity have been achived. Physics and biology measurements have been made to characterize the radiation field. 5 refs., 4 figs., 1 tab.
Date: May 1, 1985
Creator: Chu, W.T.; Curtis, S.B.; Llacer, J.; Renner, T.R. & Sorensen, R.W.
Partner: UNT Libraries Government Documents Department

Effect of negative pions on the proliferative capacity of ascites tumor cells (lymphoma) grown in vivo

Description: We have attempted to determine the relative biological effectiveness (RBE) of negative pions in the Bragg-peak region as compared to the plateau region and to gamma rays. We irradiated LAF{sub 1} mice, bearing 5-day-old lymphoma ascites tumors, in the peak and plateau regions of a 90-MeV pion beam for 40 hours in temperature-controlled holders. The animals were then sacrificed; lymphoma cells were withdrawn and titrated into adult female LAF{sub 1} mice. The proliferative capacity of the irradiated tumor cells was evaluated after 8 weeks by observing the percentage of animals developing ascites tumors. Surviving fractions were then calculated from LD{sub 50}`s of control and irradiated animals. Radiation doses in the 50 plateau region were measured with LiF dosimeters calibrated against cobalt-60 gamma rays. We calculated peak doses from those at the plateau, using a measured average peak-to-plateau ionization ratio of 1.5. Doses in the plateau region ranged from 145 to 250 rads; doses in the peak region ranged from 220 to 380 rads. The survival curve for cells irradiated in the peak region gave a D{sub 0} of 65 {plus_minus} 15 rads. The plateau points were not reliable. A replicate experiment was performed using Co{sup 60} {gamma}-rays, yielding a survival-curve D{sub 0} of 350 {plus_minus} 50 rads. If the {gamma}-ray D{sub 0} is taken as a baseline, an RBE of 5.4 {plus_minus} 1.8 is obtained for negative pions in the peak region, based on the ratio of-peak-region D{sub 0} to Co{sup 60} D{sub 0}.
Date: March 30, 1967
Creator: Feola, J.M.; Richman, C.; Raju, M.R.; Curtis, S.B. & Lawrence, J.H.
Partner: UNT Libraries Government Documents Department

Relating space radiation environments to risk estimates

Description: This lecture will provide a bridge from the physical energy or LET spectra as might be calculated in an organ to the risk of carcinogenesis, a particular concern for extended missions to the moon or beyond to Mars. Topics covered will include (1) LET spectra expected from galactic cosmic rays, (2) probabilities that individual cell nuclei in the body will be hit by heavy galactic cosmic ray particles, (3) the conventional methods of calculating risks from a mixed environment of high and low LET radiation, (4) an alternate method which provides certain advantages using fluence-related risk coefficients (risk cross sections), and (5) directions for future research and development of these ideas.
Date: October 1, 1991
Creator: Curtis, S.B.
Partner: UNT Libraries Government Documents Department

Calculating survival curves in spread-peaks of heavy ion beams and comparison with experiment

Description: In preparing for treating patients with high-energy ion beams, it is important first to determine the composition of the beam, that is, the relative mixes of the various primary and secondary particles and their LET spectra, and secondly to estimate the cell killing expected during a treatment schedule. This requires measurements of the beam composition at various depths through the spread-peak region, and a calculation of cell survival using a cell-killing model designed to accommodate the mixed LET nature of the beam in the spread-peak region. This talk presents results of an experiment in which a particle identification telescope, the BEPKLET, was used to measure the LET spectra of the primary and secondary particles at two positions in a 12-cm-spread-peak of a 585 MeV/amu neon ion beam at the Bevalac. Cell survival measurements were made at the same positions at which the LET-spectra were measured. The survival curves obtained were compared with calculations using the LPL (Lethal, Potentially Lethal) model of cell-killing. Results agree quite well at doses up to about 4 Gy. A quantity proportional to the RBE at 10% survival, when plotted against dose-averaged LET for a number of different beams and energies, appears to be a fairly good predictor of biological effect. This would not be expected if the difference in biological effect due to differences in track structure between various ions at the same LET played a significant role in modifying cell-killing in the range of LETs covered by this experiment.
Date: August 1, 1995
Creator: Curtis, S.B.; Chu, W.T.; Llacer, J.; Renner, T.R.; Rodriguez, A. & Yang, T.C.H.
Partner: UNT Libraries Government Documents Department

Ionizing radiation risks to satellite power systems (SPS) workers

Description: The radiation risks to the health of workers who will construct and maintain solar power satellites in the space environment were examined. For ionizing radiation, the major concern will be late or delayed health effects, particularly the increased risk of radiation-induced cancer. The estimated lifetime risk for cancer is 0.8 to 5.0 excess deaths per 10,000 workers per rad of exposure. Thus, for example, in 10,000 workers who completed ten missions with an exposure of 40 rem per mission, 320 to 2000 additional deaths in excess of the 1640 deaths from normally occurring cancer, would be expected. These estimates would indicate a 20 to 120% increase in cancer deaths in the worker-population. The wide range in these estimates stems from the choice of the risk-projection model and the dose-response relationsip. The choice between a linear and a linear-quadratic dose-response model may alter the risk estimate by a factor of about two. The method of analysis (e.g., relative vs absolute risk model) can alter the risk estimate by an additional factor of three. Choosing different age and sex distributions can further change the estimate by another factor of up to three. The potential genetic consequences could be of significance, but at the present time, sufficient information on the age and sex distribution of the worker population is lacking for precise estimation of risk. The potential teratogenic consequences resulting from radiation are considered significant. Radiation exposure of a pregnant worker could result in developmental abnormalities.
Date: November 1, 1980
Creator: Lyman, J.T.; Ainsworth, E.J.; Alpen, E.L.; Bond, V.; Curtis, S.B.; Fry, R.J.M. et al.
Partner: UNT Libraries Government Documents Department