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Ionizing Radiation-Induced DNA Damage and Its Repair in Human Cells

Description: DNA damage in mammalian chromatin in vitro and in cultured mammalian cells including human cells was studied. In the first phase of these studies, a cell culture laboratory was established. Necessary equipment including an incubator, a sterile laminar flow hood and several centrifuges was purchased. We have successfully grown several cell lines such as murine hybridoma cells, V79 cells and human K562 leukemia cells. This was followed by the establishment of a methodology for the isolation of chromatin from cells. This was a very important step, because a routine and successful isolation of chromatin was a prerequisite for the success of the further studies in this project, the aim of which was the measurement of DNA darnage in mammalian chromatin in vitro and in cultured cells. Chromatin isolation was accomplished using a slightly modified procedure of the one described by Mee & Adelstein (1981). For identification and quantitation of DNA damage in cells, analysis of chromatin was preferred over the analysis of "naked DNA" for the following reasons: i. DNA may not be extracted efficiently from nucleoprotein in exposed cells, due to formation of DNA-protein cross-links, ii. the extractability of DNA is well known to decrease with increasing doses of radiation, iii. portions of DNA may not be extracted due to fragmentation, iv. unextracted DNA may contain a significant portion of damaged DNA bases and DNA-protein cross-links. The technique of gas chromatography/mass spectrometry (GC/MS), which was used in the present project, permits the identification and quantitation of modified DNA bases in chromatin in the presence of proteins without the necessity of first isolating DNA from chromatin. This has been demonstrated previously by the results from our laboratory and by the results obtained during the course of the present project. The quality of isolated chromatin was tested by measurement of its ...
Date: May 12, 1999
Creator: Dizdaroglu, Miral
Partner: UNT Libraries Government Documents Department

Morphometry for alpha particle hits of critical targets in the lungs. Final technical report

Description: The objective of this study is to provide detailed data on the number, location and type of critical target cells in the airspaces and to use these data in order to make risk assessments of the health effects of radon and radon progeny in the lungs. This will be done by quantitative morphometric study of the distribution of the various cell types and mucous lining layers in the lungs. The results provide anatomically correct models for dosimetry in the rate and human airways which significantly improve the ability to do risk assessment for radon exposures by providing quantitative data for specific cell types and provide a basis for mechanism based comparison between data available in animal exposures and human epidemiology.
Date: November 1, 1998
Creator: Mercer, R.R.
Partner: UNT Libraries Government Documents Department

A Physico-Chemical Study of Some Areas of Fundamental Significance to Biophysics

Description: This report covers: Radiation Signatures; Electronic Structure of Steroids, Vitamins, and others; Laser Optogalvanic Effect; Vacuum Ultraviolet Spectroscopy, including Electron Scattering, Photochemistry, and Magnetic Circular Dichroism; and Ozone.
Date: April 1, 1999
Creator: Kumar, Devendra & McGlynn, S. P.
Partner: UNT Libraries Government Documents Department

Assessment of acute and late effects to high-LET radiation

Description: We have begun to reassess late tissue effects available from the Charged Particle Cancer Radiotherapy program at Berkeley. Our quantitative approach is limited in the analysis of these Phase I/II studies by not having equivalent patient numbers for each of the particle beams studied, by not having completely comparable follow-up times, by variations in the sizes of the fields compared, by variations in the skin scoring photographic documentation available from the patient charts, and by variations in the fractionation sizes, numbers and schedules. Despite these limitations, preliminary evidence demonstrates acute skin reactions with a shift to increasing lower dose per fraction per field for the maximum skin reactions of helium, carbon and neon ions compared to electrons. Comparisons with skin reactions from low-energy neutrons indicate that Bragg peak carbon ions (initial energy 308 MeV/nucleon) are slightly less effective than 7.5 MeV neutrons. Bragg peak neon ions (initial energy 670 MeV/nucleon) corrected for differences in reference radiation are slightly more effective than 7.5 MeV neutrons. Bragg peak silicon (initial energy 670 MeV/nucleon) result in an enhanced acute skin reaction, and a premature appearance of late effects that may indicate a significantly different mechanism of damage and/or repair.
Date: November 1, 1994
Creator: Blakely, E.A. & Castro, J.R.
Partner: UNT Libraries Government Documents Department

Statistical methodology used in analyses of data from DOE experimental animal studies

Description: This document describes many of the statistical approaches that are being used to analyze data from life-span animal studies conducted under the Department of Energy experimental radiobiology program. The methods, which are intended to be as informative as possible for assessing human health risks, account for time-related factors and competing risks, and are reasonably comparable to methods used for analyzing data from human epidemiologic studies of persons exposed to radiation. The methods described in this report model the hazard, or age-specific risk, as a function of dose and other factors such as dose rate, age at risk, and time since exposure. Both models in which the radiation risk is expressed relative to the baseline risk and models in which this risk is expressed in absolute terms are formulated. Both parametric and non-parametric models for baseline risks are considered, and several dose-response functions are suggested. Tumors in animals are not always the cause of death but instead may be found incidentally to death from other causes. This report gives detailed attention to the context of observation of tumors, and emphasizes an approach that makes use of information provided by the pathologist on whether tumors are fatal or incidental. Special cases are those in which all tumors are observed in a fatal context or in which all tumors are observed in an incidental context. Maximum likelihood theory provides the basis for fitting the suggested models and for making statistical inferences regarding parameters of these models. Approaches in which observations are grouped by intervals of time and possibly other factors are emphasized. This approach is based on iteratively reweighted least squares and uses Poisson weights for tumors considered to be fatal and binomial weights for tumors considered to be incidental.
Date: July 1, 1995
Creator: Gilbert, E.S.; Griffith, W.C. & Carnes, B.A.
Partner: UNT Libraries Government Documents Department

Calculations related to the application of neutrons, protons, negatively charged pions, and heavy ions in cancer radiotherapy

Description: From grantees conference on instrumentation technology; Washington, District of Columbia, USA (26 Sep 1973). The most significant aspects of the research conducted during the period from September 1, 1972 to August 31, 1973 on the comparative study of the use of photons, neutrons, protons, negatively charged pions, and heavy ions in cancer radiotherapy are reviewed. The survival of cultured cells was used as the test criteria. Calculations were made of radiation dose distributions in tissue-equivalent phantoms exposed to charged pions. (CH)
Date: January 1, 1973
Creator: Alsmiller, R.G. Jr.
Partner: UNT Libraries Government Documents Department

Influence of experimental end points, dose, dose rate, neutron energy, nitrogen ions, hypoxia, chromosome volume and ploidy level on RBE in Tradescantia stamen hairs and pollen

Description: From effects of neutron irradiation upon cell function; Neuherberg, F.R. Germany (22 Oct 1973). Procedures are described for irradiating Tradescantia cuttings with neutrons and x rays. Stamen hairs were scored for various mutations. Results are discussed under the following headings: experimental end points and RBE; influence of dose on RBE; effect of dose rate on RBE; influence of neutron energy on RBE; the RBE of 3.9 GeV nitrogen ions; the influence of hypoxia (OER); and the influence of chromosome volume and ploidy level on RBE; pollen abortion data. Graphs are presented to show survival curves for stamen hairs after neutron and x irradiation and neutron and x-ray dose-response curves for pink mutants, blue giant cells. and colorless mutants. (HLW)
Date: January 1, 1973
Creator: Underbrink, A.G. & Sparrow, A.H.
Partner: UNT Libraries Government Documents Department

Ninth year progress report, August 1, 1972--July 31, 1973

Description: Rats that received 100 R of in utero x irradiation on the eighteenth day of gestation survived hypothalamic electrode implantation poorly; exhibited a diminished response to hypothalamic stimulation; and showed no significant difference in their preand post-tongue radiation saccharin taste threshold. (auth)
Date: January 1, 1973
Creator: Shaber, G.S.
Partner: UNT Libraries Government Documents Department