Cellular Radiation Effects Research Articles

Enhancement of X ray induced DNA damage by pre-treatment with halogenated pyrimidine analogs

The use of the halogenated pyrimidine analogs, including bromodeoxyuridine (BrdUrd) and iododeoxyuridine (IdUrd), as potential clinical radiosensitizers is an area of renewed clinical research. Cellular radiation effects of these analogs using clinically achievable steady state plasma levels (10 −7−10 −5 M) were measured in vitro using exponentially growing Chinese hamster V79 cells. Radiation response was determined by clonogenic survival and by the production of DNA single strand (SSB) and double strand breaks (DSB) using filter elution techniques. Replacement of thymidine in DNA by BrdUrd or IdUrd was also determined. Drug exposure of BrdUrd or IdUrd for two population doublins (17 hr) prior to irradiation resulted in a progressive reduction of n̄ and D 0 compared to untreated controls over the drug dose range of 10 −7-10 −5 M. The percent thymidine replacement increased from 1% at 10 −7 M to 5% at 10 −6 M to 23% at 10−5 M. Using a 17 hr exposure at 10 −5 of BrdUrd of IdUrd, the production of SSB and DSB was increased by ≥2× and ≥1.5× respectively. No differences in the kinetics of repair of SSB and DSB were found following 3 hr of post-irradiation repair. We conclude that in this in vitro model, there appears to be a direct relationship between percent thymidine replacement, reduction of radiation survival parameters (n, D 0), and the production of DNA strand breaks in the clinically achievable dose range of these halogenated pyrimidine analogs. These filter elution assays may be adapted to in vivo studies and possibly may allow for monitoring of radiation-induced DNA damage and repair in clinical tumor specimens treated with these radiosensitizers.

Cellular Effects of Electromagnetic Radiation

Cellular Effects of Electromagnetic Radiation

Single-strand breaks can lead to complex configurations of plasmid DNA in vitro.

DNA species which migrate extremely slowly in agarose gel electrophoresis may be formed from plasmid DNA containing radiation-induced single-strand breaks (ssbs). Postirradiation heat treatment in low ionic strength buffer and subsequent incubation with Mg2+ strongly enhanced the formation of these species. Electron micrographs taken after such treatment show numerous complex configurations containing DNA material from several plasmid molecules. Less extreme formation of slowly migrating DNA occurred without postirradiation heat treatment or Mg2+ incubation when the DNA was co-precipitated with calcium phosphate in a physiologically balanced buffer and incubated under conditions used for DNA-mediated gene transfer. The data suggest that homologous pairing between single-stranded regions formed in relation to ssbs may contribute to cohesion between different molecules. The significance of the cohesion process for gene transfer experiments and cellular radiation effects is discussed.

Radiobiology of the Skin: Review of Some Effects on Epidermis and Hair

Significant doses of ionizing radiation produce an acute skin reaction characterized by erythema, epilation, and dry or moist desquamation with or without erosions. These early acute changes are dose-dependent and reflect damage to the germinative cells of the epidermis and to the cutaneous vasculature. Studies in the pig, for example, have shown that the degenerative phase of cell loss (2-3 weeks) results from reproductive failure in germinative cells and a sharp reduction in the proliferation rate of basal cell "survivors." D0 values for epidermal cells in different species generally range from 100-140 rads. Cell maturation and ascension rates in the suprabasilar layers are largely unaffected. A regenerative phase of cell replacement, characterized by sharply increased cell replication rates, occurs from the 3rd to 5th postradiation weeks. The postregenerative phase of hyperplasia reflects a temporary overshoot of cell density above control levels; a subsequent decrease in hyperplasia indicates feedback control of cellular proliferation. Postradiation changes in the highly proliferative anagen hair matrix cell populations result in hair dysplasia, slowed growth rates, impaired metabolic processes, and alopecia. Dosages of 700-800 rads or more induce some degree of permanent hair loss. G0 telogen matrix cells are 2-3 times more radioresistant than proliferating anagen matrix cells, but may "store" radiation damage for prolonged periods. Altered matrix cell uptake of amino acids, the incidence of dysplasia, and the degree of alopecia occurring after irradiation have all been used as quantitative biological end-points for the general study of cellular radiation effects, as well as studies on the enhancement of or protection against radiation damage provided by certain pharmacologic or physical agents.

Cellular radiation effects and hyperthermia: cytokinetic investigations with stationary phase yeast cells.

Wild type diploid yeast, Saccharomyces cerevisiae strain 211, was subjected to 250 kV X-rays or 50 degrees C heat treatment for 30 min or to a combination of both. X-ray exposure took place either in air or in nitrogen. Cell number, percentage of budding cells and cell cycle progression was followed for up to 12 h post irradiation. The distribution of cell cycle stages was determined by flow cytofluorometry. All treatments cause a retardation of cell division rate. Hyperthermia leads mainly to a lengthening of G1, whereas X-rays arrest the cells reversibly in G2. The effect of the combined treatment appears to be merely additive. No. selective action of hyperthermia on hypoxic cells was found.

Physical aspects of radiation sensitivity

A characteristic feature of ionizing radiation is the high energy concentration that occurs in the tracks of charged particles regardless of the level of absorbed dose. It is this feature that accounts for cellular radiation sensitivity at low doses. A survey is first given over the energies required to inactivate various microorganisms, and these energies are then related to the average number of DNA single strand and double strand breaks that are produced at the mean inactivation doses. It is pointed out that the production of DNA double strand breaks is always a single particle effect except at very high doses or in aqueous solution. However, a consideration of sigmoid dose effect curves and of the LET dependence of various biological effects indicates that a synergism of energy transfers or of radiation induced sublesions occurs over much larger distances. Individual double strand breaks cannot, therefore, be the lesions responsible for cellular radiation effects. However, they may be the sublesions that combine to produce the observed effects. The microdosimetric analysis that permits an estimation of the interaction distances of sublesions and the earlier analysis by Lea 16 are described in their essentials. A more recent analysis, based on an explicit description of the spatial correlation of energy transfers in charged particle tracks, is also discussed. This analysis utilizes the so-called “proximity functions.” The use of these functions is exemplified by the application to a recent experiment of Rossi et al. 19 where cells are exposed to pairs of deuterons with variable lateral separation.

Cellular Radiation Effects and Hyperthermia Influence of Post-exposure Incubation Conditions

Cellular Radiation Effects and Hyperthermia Influence of Post-exposure Incubation Conditions

Cellular radiation effects and hyperthermia. Influence of exposure temperature on survival of diploid yeast irradiated under oxygenated and hypoxic conditions.

Cellular radiation effects and hyperthermia. Influence of exposure temperature on survival of diploid yeast irradiated under oxygenated and hypoxic conditions.

Early macromolecular changes after release of contact inhibition by the glass bead method.

EARLY MACROMOLECULAR CHANGES AFTER RELEASE OF CONTACT INHIBITION BY THE GLASS BEAD METHODGERALD M. KOLODNY, M.D.Audio Available | Share

Ultrastructural changes in the cerebellum after focal deuteron irradiation. Cerebellar irradiation.

Previous studies have indicated only negligible damage to nerve cells of the cerebral and cerebellar cortex after irradiation with microbeams at 5000 rads or more of energy (32). A number of studies have also suggested that higher doses may selectively destroy only certain types of cells (19, 20). Consequently, focal microbeam irradiation techniques with monoenergetic particles may be particularly suitable for examining differential cellular radiosensitivities within a region of the brain containing heterogeneous cell populations. Since the small geometric configuration of such a focal field minimizes vascular and indirect abscopal effects (23, 31, 33), it also seems more likely that specific information on some of the earliest irradiation effects on nerve cell structure and function can be obtained by exposure to high dose microbeam irradiation with subsequent examination of the irradiated tissues by electron microscopy. The present investigation was undertaken with monoenergetic particles to examine in greater detail the earliest sequence of ultrastructural changes observable directly in a beam path produced by focal deuteron irradiation of the cerebellum in adult mice. This particular region of the central nervous system was selected for more detailed examination since previously reported findings indicated a variety of differential cellular radiation effects between granule and Purkinje cells exposed to similar high dose microbeam irradiation (19). The examination of various early sequential ultrastructural changes was facilitated in the present study by comparative observations of damage to nerve cells and associated vascular and glial elements located directly in the beam path as compared to the appearance of adjacent non-irradiated normal cells. The specific aim of this study was to examine in greater detail the sequence of ultrastructural changes in neurons, blood vessels, and glial elements in the beam path from 5 minutes to 10 days after focal irradiation of the brain.

Response of Isolated Leukocyte Lysosomes to Gamma Irradiation

The recognition of the lysosome as a distinct intracellular structure has been followed by several attempts to elucidate the possible role of this organelle in the production or exacerbation of cellular radiation damage. The lysosome is a natural subject for such investigations, since it is essentially a depot of hydrolytic enzymes segregated from the rest of the cell by a single bounding membrane. The properties of lysosomes have been recently reviewed (1). Studies of the lysosomal enzyme acid phosphatase in cells collected from the peritoneal cavity of rats bearing induced peritoneal exudates 1 to 10.5 hours after whole-body X-irradiation (800 R) indicated an increase in the amount of this enzyme and suggested the possibility of lysosomal damage. Other cells and tissues of irradiated animals have also been found to possess slightly increased or labilized lysosomal enzyme content (2-9). The interpretation of these results is often complicated, however; there is evidence that the apparent increase in enzyme activity observed after whole-body irradiation may be the result of changes in cell population within certain tissues (10), destruction of lymphatic tissues (9), or increased endocrine activity (7). In the case of the peritoneal cell study cited above, the analysis is further complicated by the occurrence of early postirradiation changes in the net permeability of blood vessels in or bordering on the peritoneal cavity.2 Investigations of isolated lysosomes have not provided a complete answer to the question of the extent of lysosomal involvement in cellular radiation effects. Although high doses are usually required to elicit release of hydrolytic enzymes in vitro (11), lysosomes isolated from different tissues respond differently to ionizing radiation. Lysosomes isolated from rat liver showed increased reaction with enzyme

Cellular Radiation Effects

A critical review is given of radiation effects on cytological structures: mitochondria, lysosomes, microsomes, cytoplasmic soluble components, cell membranes, and nucleus. The implications of these changes for the analysis of radiation effects upon biological functions are discussed. The functions studied are cell growth, cell division, movements and differentiation.