Showing papers in "Radiation Research in 1989"
1,443 citations
1,053 citations
TL;DR: Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects, with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children.
Abstract: The thyroid gland is highly sensitive to the carcinogenic effects of ionizing radiation. Previously, we reported a significant increase of thyroid cancer and adenomas among 10,834 persons in Israel who received radiotherapy to the scalp for ringworm. These findings have now been extended with further follow-up and revised dosimetry. Overall, 98 thyroid tumors were identified among the exposed and 57 among 10,834 nonexposed matched population and 5392 sibling comparison subjects. An estimated thyroid dose of 9 cGy was linked to a fourfold (95% Cl = 2.3-7.9) increase of malignant tumors and a twofold (95% Cl = 1.3-3.0) increase of benign tumors. The dose-response relationship was consistent with linearity. Age was an important modifier of risk with those exposed under 5 years being significantly more prone to develop thyroid tumors than older children. The pattern of radiation risk over time could be described on the basis of a constant multiplication of the background rate, and an absolute risk model was not compatible with the observed data. Overall, the excess relative risk per cGy for thyroid cancer development after childhood exposure is estimated as 0.3, and the absolute excess risk as 13 per 10(6) PY-cGy. For benign tumors the estimated excess relative risk was 0.1 per cGy and the absolute risk was 15 per 10(6) PY-cGy.
274 citations
TL;DR: An overview of the properties and applications of PDT is provided, including information and data related to drug development, photochemistry, subcellular targets, in vivo responses, and clinical trials of PDT.
Abstract: Photodynamic therapy (PDT) is the treatment of malignant lesions with visible light following the systemic administration of a tumor-localizing photosensitizer. Pharmacological and photochemical properties of the photosensitizer are combined with precise delivery of laser-generated light to produce a treatment which can offer selective tumoricidal action. Hematoporphyrin derivative (HD) and a purified component called Photofrin II are currently being used in clinical PDT. Initial patient results have been encouraging, and considerable interest has developed in the synthesis and evaluation of new photosensitizers with improved photochemical and pharmacological characteristics. In addition, there has been a gradual increase in knowledge related to in vitro and in vivo mechanisms of action of PDT. This report provides an overview of the properties and applications of PDT. Information and data related to drug development, photochemistry, subcellular targets, in vivo responses, and clinical trials of PDT are presented.
256 citations
TL;DR: It is concluded that 31P-MRS can detect changes in tumor bioenergetics brought about by changes in tumors oxygenation, and the close correlation between oxygenation and energy status suggests that the microcirculation in FSaII tumors yields an O2-limited energy metabolism.
Abstract: Size-dependent changes in therapeutically relevant and interrelated metabolic parameters of a murine fibrosarcoma (FSaII) were investigated in vivo using conscious (unanesthetized) animals and tumor sizes less than or equal to 2% of body weight Tumor pH and bioenergetics were evaluated by 31P nuclear magnetic resonance spectroscopy (31P-MRS), and tumor tissue oxygen tension (pO2) distribution was examined using O2-sensitive needle electrodes During growth FSaII tumors showed a progressive loss of phosphocreatine (PCr) and nucleoside triphosphate (NTP) with increasing inorganic phosphate (Pi) and phosphomonoester (PME) signals Ratios for PCr/Pi, PME/Pi, NTP/Pi, and phosphodiester/inorganic phosphate (PDE/Pi) as well as pH determined by 31P-NMR (pHNMR) and the mean tissue pO2 progressively declined as the tumors increased in size The only relevant ratio increasing with tumor growth was PME/NTP When the mean tissue pO2 value was plotted against pHNMR, NTP/Pi, PCr/Pi, PME/Pi, and PDE/Pi for tumor groups of similar mean volumes, a highly significant positive correlation was observed There was a negative correlation between mean tumor tissue pO2 values and PME/NTP From these results we concluded that 31P-MRS can detect changes in tumor bioenergetics brought about by changes in tumor oxygenation Furthermore, the close correlation between oxygenation and energy status suggests that the microcirculation in FSaII tumors yields an O2-limited energy metabolism Finally, a correlation between the proportion of pO2 readings between 0 and 25 mmHg and the radiobiologically hypoxic cell fraction in FSaII tumors was observed The latter finding might be of particular importance for radiation therapy
138 citations
TL;DR: It is suggested that nonperfusion of apparently normal lung acini is a major factor in late-phase deaths in those mouse strains which show little or no fibrosis.
Abstract: Strain differences in the intermediate and late phases of the radiation response of mouse lung were investigated histologically. The proportion of lung impairment in mice at 28 and 52 weeks postirradiation and in mice dying of respiratory insufficiency was assessed by scoring lung acini as nonfunctional due to lesions which obstructed airflow, or open and presumably functional. The nine strains tested were divided into three groups on the basis of the late fibrotic response. Group 1 mice, three C57 strains, developed extensive contracted fibrosis and usually showed enough damage to explain late deaths. Group 2, SWR, A, and BALB/c strains, developed foci of contracted fibrosis. Group 3, CBA and two C3H strains, did not form fibrotic scars. Mice in Groups 2 and 3 that died with no pleural effusions appeared to have insufficient late lung damage to account for respiratory distress. Problems with pulmonary blood flow were indicated by evidence of loss of fine vasculature and right ventricular hypertrophy. In nondistressed, late-stage mice in Groups 2 and 3, loss of capillary perfusion in lung parenchyma free of obvious lesions was demonstrated by infusion of colloidal carbon. In one strain, A, an estimate of the proportion of nonperfused lung was mademore » on distressed late-stage mice. Almost 50% of lung acini were nonfunctional as a result of nonperfusion, and an additional 9% of acini were nonfunctional due to lesions obstructing ventilation. It is suggested that nonperfusion of apparently normal lung acini is a major factor in late-phase deaths in those mouse strains which show little or no fibrosis.« less
132 citations
TL;DR: The results confirm that Nicotinamide significantly enhances the radiation damage in this tumor when given as a single intraperitoneal injection 90 min before irradiation, and show that nicotinamide does not directly sensitize hypoxic cells to radiation either in vitro or in vivo.
Abstract: Nicotinamide has been shown to sensitize tumors to radiation in preference to normal tissues. We have extended our studies to examine the mechanism responsible for this radiosensitization, using the EMT6 tumor model. Our results confirm that nicotinamide (1000 mg/kg) significantly enhances the radiation damage in this tumor when given as a single intraperitoneal injection 90 min before irradiation. The data also show that nicotinamide does not directly sensitize hypoxic cells to radiation either in vitro or in vivo. Excising tumors immediately after irradiation and exposing them to nicotinamide (7 mM) for 24 h similarly failed to increase the radiation damage, implying that nicotinamide does not inhibit the repair of radiation-induced potentially lethal damage. Nicotinamide did, however, produce a decrease in the binding of [14C]-misonidazole in tumors, consistent with a reduction in the degree of tumor hypoxia. There was also an increase in mean tumor cell fluorescence of Hoechst 33342 in nicotinamide-treated mice compared to that of controls, suggesting that the increase in tumor oxygenation was probably a consequence of an increase in tumor blood perfusion.
131 citations
TL;DR: The degree of lung impairment in mice dying of respiratory insufficiency was assessed by scoring lung acini as nonfunctional or open and presumably functional, and over 70% of acini were nonfunctional as a result of airflow obstruction.
Abstract: Strain differences in the radiation response of mouse lung during the early phase (before 28 weeks postirradiation) were investigated histologically. The nine strains tested were divided into three groups on the basis of the nature of the edema present, the occurrence of hyaline membranes, and the presence of fibrosis. Group 1 mice, three C57 strains, developed hyaline membranes, focal fibrosis, and a protein-rich edema containing fibrin. Group 3, CBA and two C3H strains, had only a protein-poor edema with little fibrin and developed no visible fibrosis. Group 2 mice had both types of edema and small quantities of focal fibrosis. The degree of lung impairment in mice dying of respiratory insufficiency was assessed by scoring lung acini as nonfunctional or open and presumably functional. Over 70% of acini were nonfunctional as a result of airflow obstruction. This was considered sufficient to account for death. Carbon perfusion immediately before sacrifice indicated that all types of lesions were at least partially perfused with blood. Pleural effusions were found in some individuals of two strains. The proportion of nonfunctional acini was similar in mice of the same strain with and without effusions, which would not be expected if the effusions contributed appreciably to respiratory distress in the early phase.
120 citations
TL;DR: Gas chromatography-mass spectrometry with selected-ion monitoring was used to study radiation-induced damage to DNA and 6-azathymine and 8-azaadenine were found to be suitable internal standards for quantitative measurement of base damage in DNA.
Abstract: Gas chromatography-mass spectrometry with selected-ion monitoring was used to study radiation-induced damage to DNA. Quantitative analysis of modified purine and pyrimidine bases resulting from exposure to ionizing radiation using this technique is dependent upon the selection of appropriate internal standards and calibration of the mass spectrometer for its response to known quantities of the internal standards and the products of interest. The compounds 6-azathymine and 8-azaadenine were found to be suitable internal standards for quantitative measurements of base damage in DNA. For the purpose of calibration of the mass spectrometer, relative molar response factors for intense characteristics ions were determined for the trimethylsilyl derivatives of 5-hydroxyuracil, thymine glycol, and 5,6 dihydrothymine using 6-azathymine, and for the trimethylsilyl derivatives of 4,6-diamino-5-formamidopyrimidine, 8-hydroxyguanine using 8-azaadenine. Accurate measurements of the yield of radiation-induced modifications to the DNA bases is also dependent upon two chemical steps in which the purines and pyrimidines are released from the sugar-phosphate backbone and the derivatized to make them volatile for gas chromatography. The completeness of these reactions, in addition to assessing the stability of the modified DNA bases in acid and their trimethylsilylated derivatives over the time necessary to complete the experimental analysis, was also examined.
117 citations
TL;DR: Rat embryo cells at various stages of oncogenic transformation are obtained by a combination of X irradiation and transfection with the ras and the myc oncogenes, and incorporation of the two oncogens appears to lead to a higher degree of radioresistance.
Abstract: Rat embryo cells at various stages of oncogenic transformation are obtained by a combination of X irradiation and transfection with the ras and the myc oncogenes. Transfection with either the ras or the myc oncogenes can lead to increased radioresistance, relative to the parental cells. X-ray-transformed clones of the transfected cells do not show additional alteration in radioresponse. Incorporation of the two oncogenes appears to lead to a higher degree of radioresistance.
114 citations
TL;DR: L'auteur discute l'action de l'hyperthermie sur les cellules de Mammiferes et des nombreux problemes qui sont lies.
Abstract: L'auteur discute l'action de l'hyperthermie sur les cellules de Mammiferes et des nombreux problemes qui sont lies. Il suggere que les principaux effets cellulaires de l'hyperthermie resultent de la denaturation et de l'agregation des proteines dans la cellule et ce phenomene est responsable de la mort cellulaire de la radiosensibilisation par la chaleur que la chaleur est administree avant l'irradiation
TL;DR: The rate of development of radiation resistance is shown to be similar when either cell survival or DNA unwinding is used as an end point, and 10-h cultures show a homogeneous radiation response intermediate between that of monolayers and spheroids.
Abstract: Chinese hamster V79 cells grown for several hours in suspension culture form spheroids which are more resistant to killing by ionizing radiation than cells grown on petri dishes, a phenomenon known as the contact effect. Previous results using the alkali-unwinding assay as a measure of DNA damage have implicated differences in DNA conformation as contributing to this effect; spheroid DNA denatures more slowly in dilute alkali than monolayer DNA, perhaps due to the presence of constraints to DNA unwinding. In this paper, the rate of development of radiation resistance is shown to be similar when either cell survival or DNA unwinding is used as an end point. At the midpoint for development of resistance, approximately 10 h, the unwinding kinetics indicate that either half of the cells contain constraints to DNA unwinding, or half of the DNA in all of the cells contains constraints. The latter explanation appears more likely since all cells seem to develop these constraints at the same rate, regardless of position in the cell cycle or the degree of contact with other cells. Results using the microelectrophoresis assay to measure damage to individual nuclei confirm the fact that 10-h cultures show a homogeneous radiation response intermediatemore » between that of monolayers and spheroids. Incubation of cells at room temperature or in the presence of drugs which inhibit cell cycle progression prevents full development of the contact effect. Conversely, incubation of cells in medium containing inhibitors of polyamine synthesis, adenylcyclase, glutathione synthesis, poly(ADP-ribose)polymerase, topoisomerase II, or cell-cell communication does not inhibit development of the contact effect as measured by DNA-unwinding kinetics.« less
TL;DR: The effect of 60Co gamma radiation on DNA methylation was studied in four cultured cell lines as discussed by the authors, where a dose-dependent decrease in 5-methylcytosine was observed at 24, 48, and 72 h postexposure to 0.5-10 Gy.
Abstract: The effect of 60Co gamma radiation on DNA methylation was studied in four cultured cell lines. In all cases a dose-dependent decrease in 5-methylcytosine was observed at 24, 48, and 72 h postexposure to 0.5-10 Gy. Nuclear DNA methyltransferase activity decreased while cytoplasmic activity increased in irradiated (10 Gy) V79A03 cells as compared to controls. No DNA demethylase activity was detected in the nuclei of control or irradiated V79A03 cells. Additionally, gamma radiation resulted in the differentiation of C-1300 N1E-115 cells, a mouse neuroblastoma line, in a dose- and time-dependent manner. These results are consistent with the hypothesis that (1) genes may be turned on following radiation via a mechanism involving hypomethylation of cytosine and (2) radiation-induced hypomethylation results from decreased intranuclear levels of DNA methyltransferase.
TL;DR: Site-specific estimates of cancer mortality in the years 1950-1985, based on these new doses of DS86, are compared with those using the T65DR doses, which do not change the list of radiation-related cancers.
Abstract: As a result of the reassessment of the A-bomb dosimetry, new (DS86) doses were calculated in 1986. In this paper, site-specific estimates of cancer mortality in the years 1950-1985, based on these ...
TL;DR: It is concluded from the total data base that not only the absolute increment in nuclear protein mass must be taken into account but also the duration of the binding expressed in the rate of recovery must be take into account.
Abstract: The role of a heat-induced increase in nuclear protein mass in killing of cells by hyperthermia was investigated jointly by two groups that had previously reported apparently conflicting results. A...
TL;DR: The results indicate that there are no saturation effects in the decay of 125IUdR in the DNA of V79 cells and that each of the two steps involved in the 125I decay is equally effective in causing biological damage.
Abstract: The toxic effects of the short-lived (T 1/2 = 13.2 h) Auger-electron-emitting isotope 123I, incorporated in the form of 123IUdR into the DNA of V79 cells in vitro, have been investigated and compared to those of 125IUdR. For the concentrations tested, the rate of incorporation of 123IUdR at any time is proportional to the concentration of extracellular radioactivity. The curve for survival of clonogenic cells decreases exponentially and exhibits no shoulder at low doses. The mean lethal dose (D37) to the nucleus is 79 +/- 9 cGy and is about the same as that obtained previously with 125IUdR. However, the total number of decays needed to produce this D37 with 123IUdR is about twice that required with 125IUdR, approximately equal to the ratio of the energy deposited in microscopic volumes by 125I and 123I, respectively. This correlation suggests that nuclear recoil, electronic excitation, and chemical transmutation are probably of minor importance to the observed biological toxicity with either isotope. The results also indicate that there are no saturation effects in the decay of 125IUdR in the DNA of V79 cells (i.e., all of the emitted energy is biologically effective) and that each of the two steps involved in the 125I decay is equally effective in causing biological damage.
TL;DR: The effect of BrdU incorporation on cell radiosensitivity as well as on the induction of DNA double-strand breaks (DSB) and chromosome damage by radiation was studied in CHO cells, suggesting an increase in the radiosensitivity of cells grown in the presence ofBrdU.
Abstract: The effect of BrdU incorporation on cell radiosensitivity as well as on the induction of DNA double-strand breaks (DSB) and chromosome damage by radiation was studied in CHO cells. Induction of DNA DSB was measured by the nonunwinding filter elution technique and damage at the chromosome level was visualized and scored in G1 cells using the technique of premature chromosome condensation. The results indicated an increase in the radiosensitivity of cells grown in the presence of BrdU. Although sensitization was observed both in cells irradiated in the exponential phase and in cells irradiated in the plateau phase of growth, the degree of sensitization was greater in exponentially growing cells for the same degree of thymidine replacement by BrdU in the DNA. It is hypothesized that this indicates the possible importance of chromatin structure at the time of irradiation and/or the importance of chromatin conformation changes after irradiation in the expression of radiation-induced potentially lethal damage i...
TL;DR: In pathogen-free mice, but not standard conventionally housed laboratory rodents, two distinctly different modes of early radiation lethality can be identified by modifying the irradiation technique (total-body versus abdominal irradiation) or by therapeutic intervention such as rescue of total-body-irradiated mice with syngeneic bone marrow or spleen.
Abstract: In pathogen-free mice, but not standard conventionally housed laboratory rodents, two distinctly different modes of early radiation lethality can be identified by modifying the irradiation technique (total-body versus abdominal irradiation) or by therapeutic intervention such as rescue of total-body-irradiated mice with syngeneic bone marrow or spleen. While damage to the gastrointestinal tract is usually designated as the predominant cause of death occurring within 10 days of radiation exposure, it was demonstrated that damage to the hematopoietic/lymphopoietic system can result in animal lethality over the same period as the gastrointestinal syndrome and that this target cell population is more radiation-sensitive than the gastrointestinal epithelium.
TL;DR: In this paper, combined analyses of mortality in workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Nuclear Weapons Plant are presented, and the results strengthen support for the conclusion that estimates obtained through extrapolation from high-dose data do not seriously underestimate risks of lowdose exposure, but leave open the possibility that extrapolation may overestimate risks.
Abstract: An important objective of studies of workers exposed occupationally to chronic low doses of ionizing radiation is to provide a direct assessment of health risks resulting from this exposure. This objective is most effectively accomplished by conducting combined analyses that allow evaluation of the totality of evidence from all study populations. In this paper, combined analyses of mortality in workers at the Hanford Site, Oak Ridge National Laboratory, and Rocky Flats Nuclear Weapons Plant are presented. These combined analyses provide no evidence of a correlation between radiation exposure and mortality from all cancer or from leukemia. Of 11 other specific types of cancer analyzed, multiple myeloma was the only cancer found to exhibit a statistically significant correlation with radiation exposure. Estimates of the excess risk of all cancer and of leukemia, based on the combined data, were negative. Upper confidence limits based on the combined data were lower than for any single population, and were similar to estimates obtained from recent analyses of A-bomb survivor data. These results strengthen support for the conclusion that estimates obtained through extrapolation from high-dose data do not seriously underestimate risks of low-dose exposure, but leave open the possibility that extrapolation may overestimate risks.
TL;DR: To explore the effect of the Auger electron emitter 125I attached to a DNA intercalator, 125I- and 127I-labeled 3-acetamido-5-iodoproflavine (AIP) is synthesized and the uptake, intracellular distribution, and radiotoxicity of A125IP in Chinese hamster V79 cells is examined.
Abstract: To explore the effect of the Auger electron emitter 125I attached to a DNA intercalator, we have synthesized 125I- and 127I-labeled 3-acetamido-5-iodoproflavine (AIP) and have examined the uptake, intracellular distribution, and radiotoxicity of A 125IP in Chinese hamster V79 cells. After incubation with AIP, the nuclei of V79 cells become fluorescent. Uptake of A 125IP is directly proportional to its extracellular radioactive concentration and reaches a plateau at about 10 h. Of the cell-associated radioactivity, 60% is retained by the cells after extensive washing. When the survival of V79 cells is plotted as a function of radioactive cell content, the curve has no shoulder with a mean lethal dose (DN) of about 1.3 Gy to the cell nucleus. Because the DN of these cells when irradiated with 250 kVp X rays is 5.8 Gy, the relative biological effectiveness (RBE) of A 125IP is about 4.5. The dependence of the RBE values on the localization of the Auger emitter is discussed on the basis of our extended studies...
TL;DR: There is a considerable variation in the yields of OH radicals with time at the highest energies, but at the maximum LET the OH radical yields are nearly invariant with time after about 10 ns.
Abstract: Formic acid solutions of 1, 10, 100, and 1000 mM have been irradiated with 4He ions of 5 to 25 MeV, and the production of OH radicals has been determined by measuring the yield of CO2. The differential OH radical yields were obtained from the observed energy dependencies; with 25 MeV 4He ions they range from 1.91 to 3.48 molecules/100 eV for formic acid concentrations of 1 to 1000 mM, respectively. The OH radical yields decrease with decreasing particle energy, and at the maximum LET (230 eV/nm) they range from 0.30 at 1 mM to 0.82 molecules/100 eV at 1000 mM. These values are only 15 to 20% of that found with fast electrons. The OH radical yields are relatively more dependent on formic acid concentration at higher 4He ion energies. The average time dependencies of the OH radical from 7.7 ns to 7.7 microseconds were estimated from the formic acid concentration dependencies at various 4He energies. In terms of absolute yields, there is a considerable variation in the yields of OH radicals with time at the highest energies, but at the maximum LET the OH radical yields are nearly invariant with time after about 10 ns.
TL;DR: The effects of light activation of the tumor photosensitizer dihematoporphyrin ether (DHE) were studied in the microcirculation of the rat cremaster muscle to account for the mechanism of action of photodynamic therapy.
Abstract: The effects of light activation of the tumor photosensitizer dihematoporphyrin ether (DHE) were studied in the microcirculation of the rat cremaster muscle. Arterioles and venules in an implanted chondrosarcoma were studied by in vivo television microscopy and were compared to normal vessels of the same size elsewhere in the preparation and in control preparations. Activation with green light (530-560 nm, 200 mW/cm2, 120 J/cm2) 48 h after intraperitoneal injection of DHE (10 mg/kg body wt) resulted in significant narrowing of diameters of red blood cell columns in tumor arterioles and venules. The response in normal and control arterioles and venules was not significantly different from that seen in the tumor vessels except that the control arterioles did not remain significantly constricted during the treatment period. Treatment resulted in stasis of blood flow in 90% of tumor and normal arterioles at the completion of light activation. In venules, stasis of blood flow was observed in 75% of tumor and 70% of normal vessels. Vasoconstriction was the primary response in arterioles, while thrombosis predominated in venules. Morphologic assessment of light-activated vessels in the cremaster preparation by transmission electron microscopy revealed platelet aggregation with damage to endothelial cells and smooth muscle cells. Perivascular effects observed included interstitial edema and damage to skeletal muscle cells. In the tumor-bearing preparation, no direct cytotoxic effect on the tumor cells was shown. The surrounding vessels exhibited similar vascular stasis, but the lining cells appeared minimally affected. Photoactivation of DHE results in significant changes in the microcirculation which lead to stasis of blood flow. In this model, the response was similar for the normal microvasculature and for the microcirculation of an implanted chondrosarcoma. These effects may account, in part, for the mechanism of action of photodynamic therapy.
TL;DR: The final analysis of an experiment to study the interaction of a beam of 670A MeV neon ions incident on a water column set to different thicknesses finds the fluence of particles of a given charge was obtained and normalized to the incident beam intensity.
Abstract: We present the final analysis of an experiment to study the interaction of a beam of 670A MeV neon ions incident on a water column set to different thicknesses. The atomic number Z (and, in some cases, the isotopic mass A) of primary beam particles and of the products of nuclear interactions emerging from the water column close to the central axis of the beam was obtained for nuclei between Be (Z = 4) and Ne (Z = 10) using a time-of-flight telescope to measure the velocity and a set of silicon detectors to measure the energy loss of each particle. The fluence of particles of a given charge was obtained and normalized to the incident beam intensity. Corrections were made for accidental coincidences between multiple particles triggering the TOF telescope and for interactions in the detector. The background due to beam particles interacting in beam line elements upstream of the detector was calculated. Sources of experimental artifacts and background in particle identification experiments designed to characterize heavy ion beams for radiobiological research are summarized, and some of the difficulties inherent in this work are discussed. Complete tables of absolutely normalized fluence spectra as a function of LET are included for reference purposes.
TL;DR: The data suggest that the ability of ACE inhibitors to ameliorate radiation-induced pulmonary endothelial dysfunction is not unique to captopril, rather it is a therapeutic action shared by other members of this class of compounds.
Abstract: The purpose of this study was to evaluate the angiotensin converting enzyme (ACE) inhibitor CL242817 as a modifier of radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a single dose of60 Co γ rays (0-30 Gy) to the right hemithorax. CL242817 was administered in the feed continuously after irradiation at a regimen of 60 mg/kg/day. Pulmonary endothelial function was monitored by lung ACE activity, plasminogen activator (PLA) activity, and prostacyclin ( PGI2) and thromboxane ( TXA2) production. Pulmonary fibrosis was evaluated by lung hydroxyproline (HP) content. Lung ACE and PLA activities decreased with increasing radiation dose, and cotreatment with CL242817 significantly ameliorated both responses. CL242817 dose-reduction factors (DRF) were 1.3-1.5 for ACE and PLA activity. Lung PGI2 and TXA2 production increased with increasing radiation dose, and CL242817 almost completely prevented both radiation responses. The slope of the radiation dose-resp...
TL;DR: Based on the numbers of nuclear aberrations, the dose response did not differ significantly from that observed at 24 h in parotid gland irradiated in vivo, and the similar rapid response under the two conditions shows that apoptosis of irradiatedParotid serous cells is a direct expression of interphase cell death.
Abstract: Organ cultures of rhesus parotid tissue in medium enriched with homologous serum and supplemented with low levels of isoproterenol were irradiated with single photon doses of 2.5, 5.0, 7.5, 10.0, 12.5, or 15.0 Gy. Following irradiation, the tissue was incubated while being agitated for 24 h; then it was fixed in formalin. Microscopically, death of serous acinar cells was seen in areas unaltered by autolysis. Based on the numbers of nuclear aberrations, the dose response did not differ significantly from that observed at 24 h in parotid gland irradiated in vivo. The similar rapid response under the two conditions shows that apoptosis of irradiated parotid serous cells is a direct expression of interphase cell death.
TL;DR: The elevated radiation sensitivity of chromatin relaxed by acetylation is in good agreement with previous results on chromatin expanded by histone H1 depletion and is discussed in light of the variation of radiation sensitive of whole cells in the cell cycle which incorporates repair.
Abstract: V-79 Chinese hamster lung fibroblasts exposed to 5 mM n-sodium butyrate were irradiated with 60Co gamma rays and cell survival was determined by the cell colony assay. In a separate set of experiments the acetylated chromatin obtained from these cells was irradiated and the change of molecular weight of the DNA was evaluated by alkaline sucrose density centrifugation. At a survival level of 10(-2) to 10(-4) cells exposed to butyrate were found to be 1.3-1.4 times more radiosensitive than control cells. Exposure of isolated chromatin to 100 Gy of 60Co gamma irradiation generated 0.9 +/- 0.03 single-strand breaks (ssb) per 10 Gy per 10(8) Da and 2.0 +/- 0.3 ssb/10 Gy/10(8) Da for control and acetylated chromatin, respectively. The elevated radiation sensitivity of chromatin relaxed by acetylation is in good agreement with previous results on chromatin expanded by histone H1 depletion. Packing and accessibility of DNA in chromatin appear to be major factors which influence the radiation sensitivity. The intrinsic radiation sensitivity of chromatin in various packing states is discussed in light of the variation of radiation sensitivity of whole cells in the cell cycle which incorporates repair.
TL;DR: It is reported that statistically significant (at P greater than 0.999) enhancement of transformation response by TPA is reported in cells exposed to 2.45-GHz microwaves (SAR = 4.4 W/kg).
Abstract: C3H/10T1/2 cells were exposed to 2.45-GHz microwaves for 24 h and/or 1.5 Gy of 238-kVp X rays at 3.75 Gy/min. Transformation frequency and cell survival were measured with or without postirradiation addition of the tumor promoter tetradecanoyl-phorbol-13-acetate (TPA) at 0.1 microgram/ml. We previously reported (Carcinogenesis 6,859-864, 1985) an enhancement of transformation frequency when 10T1/2 cells exposed to a special sequence of microwaves and X rays were subsequently cultured in TPA. The same sequence of microwaves and X rays without promotion resulted in a transformation response similar to that induced by X rays alone. We now report statistically significant (at P greater than 0.999) enhancement of transformation response by TPA in cells exposed to 2.45-GHz microwaves (SAR = 4.4 W/kg). Microwaves alone had no effect on transformation. Plating efficiency and cell survival were not affected by TPA or microwave treatments.
TL;DR: This study clearly shows that over the range of neutron energies typically seen by nuclear power plant workers and individuals exposed to the atomic bombs in Japan, a wide range of RBE values needs to be considered when evaluating the neutron component of the effective dose.
Abstract: The relative biological effectiveness (RBE) of a range of neutron energies relative to 250-kVp X rays has been determined for oncogenic transformation and cell survival in the mouse C3H 10T 1/2 cell line. Monoenergetic neutrons at 0.23, 0.35, 0.45, 0.70, 0.96, 1.96, 5.90, and 13.7 MeV were generated at the Radiological Research Accelerator Facility of the Radiological Research Laboratories, Columbia University, and were used to irradiate asynchronous cells at low absorbed doses from 0.05 to 1.47 Gy. X irradiations covered the range 0.5 to 8 Gy. Over the more than 2-year period of this study, the 31 experiments provided comprehensive information, indicating minimal variability in control material, assuring the validity of comparisons over time. For both survival and transformation, a curvilinear dose response for X rays was contrasted with linear or nearly linear dose responses for the various neutron energies. RBE increased as dose decreased for both end points. Maximal RBE values for transformation ranged from 13 for cells exposed to 5.9-MeV neutrons to 35 for 0.35-MeV neutrons. This study clearly shows that over the range of neutron energies typically seen by nuclear power plant workers and individuals exposed to the atomic bombs in Japan, a wide range of RBE values needs to be considered when evaluating the neutron component of the effective dose. These results are in concordance with the recent proposals in ICRU 40 both to change upward and to vary the quality factor for neutron irradiations.
TL;DR: It is indicated that high-energy iron particles are more toxic than other qualities of radiation and similar mechanisms mediate the behavioral toxicity of gamma photons and high- energy iron particles.
Abstract: Conditioned taste aversion was used to evaluate the behavioral toxicity of exposure to high-energy iron particles (56Fe, 600 MeV/amu) in comparison to that of gamma photons (60 Co), high-energy electrons, or fission neutrons. Exposure to high-energy iron particles (5-500 cGy) produced a dose-dependent taste aversion with a maximal effect achieved with a dose of 30 cGy. Gamma photons and electrons were the least-effective stimuli for producing a conditioned taste aversion, with a maximal aversion obtained only after exposure to 500 cGy, while the effectiveness of fission neutrons was intermediate to that of photons and iron particles, and a maximal aversion was obtained with a dose of 100 CGy. In the second experiment, rats with lesions of the area postrema were exposed to iron particles (3- cGY), but failed to acquire a taste aversion. The results indicate that (1) high-energy iron particles are more toxic than other qualities of radiation and (2) similar mechanisms mediate the behavioral toxicity of gamma photons and high-energy iron particles.
TL;DR: It is reported that whole-body X irradiation induces MT-1 mRNA transcription and protein expression and accumulation in liver but not in kidney or spleen, suggesting that these agents may act through the mediation of tissue-specific factors.
Abstract: Metallothioneins (MTs) are induced in cultured cells and experimental animal tissues by a variety of chemical agents. We report that whole-body X irradiation (1 to 80 Gy) induces MT-1 mRNA transcription and protein expression and accumulation in liver but not in kidney or spleen. The degree of induction was comparable to maximum levels achieved after treatment with metal salts, but the peak of MT-1 mRNA and protein accumulation was approximately 10 h later than with treatment with metal salts and remained high for an extended period. Because of the lack of induction of MT-1 by X rays in cultured cells, and the similarity of the tissue pattern of MT induction between X rays and other agents that also do not induce MT expression in cultured cells, it appears that these agents may act through the mediation of tissue-specific factors. The implications of radiation-induced metallothionein synthesis and organ-specific resistance to cellular damage are discussed.