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D Ewing

Publications and source records attributed to D Ewing.

At least 37 records · Page 2Linked to original sources
PubMed1991

Do.OH scavenger secondary radicals protect by competing with oxygen for cellular target sites?

Recently, using Chinese hamster V79 cells, we found no relationship between the level of protection and the overall rate for .OH removal [Ewing and Walton, Radiat. Res. 126, 187-197 (1991)]. We offered several possible interpretations for this observation, including that the scavengers may actually have multiple ways to protect, ways that would occur in addition to, or instead of, simple .OH removal. With bacterial spores, we had noted that protection occurs only with those .OH scavengers that are able to react and form secondary, reducing radicals (alpha-hydroxy radicals, RCOH), and we suggested that protection might occur if these radicals reduced cellular radical sites in competition with (damaging) reactions of O2. We have now tested that hypothesis with four .OH scavengers (DMSO, ethanol, glycerol, and methanol), and Chinese hamster V79 cells, irradiated while equilibrated with 0.9% O2 and 100% O2; our recent experiments with these scavengers in air provide data for a third O2 concentration. If these scavengers protect in vitro mammalian cells by forming secondary reducing radicals which compete with O2 for damaged cellular sites, we expect that when we reduce the O2 concentration, we will concomitantly reduce the scavenger concentrations needed for protection. If the proposed competition occurs, we expect the scavenger concentrations for 50% maximum effect to occur in the ratio of the three O2 concentrations used approximately 1:20:100. We found no evidence for such a competition as the mechanism of protection for these four .OH scavengers.

Animals↗
PubMed1991

Radiation protection of in vitro mammalian cells: effects of hydroxyl radical scavengers on the slopes and shoulders of survival curves.

We have tested several chemical compounds, characterized and widely used as hydroxyl radical (.OH) scavengers, for their effects on the radiation sensitivity of Chinese hamster V79 cells irradiated in air or nitrogen. Our purpose is to reexamine the proposed relationship between the level of protection and the rates at which the scavengers react with .OH. We found that the additives can have two apparently independent effects on the shape of survival curves: a reduction in sensitivity (i.e., "protection," a decrease in the value of k) and an increase in the size of the shoulder of the survival curve (an increase in the value of Dq). We measured intracellular scavenger concentrations, and, using these values in our analysis, we found that neither of the two effects is correlated with the rates at which the scavengers react with .OH. Although these results could mean that .OH do not cause lethal damage, the interpretation we believe most probably correct is that these scavengers protect in multiple ways. The protection would occur in addition to or instead of simple .OH removal.

Animals↗
PubMed1990

Cardiovascular response of a continuous variable rate alfentanil infusion for abdominal aortic surgery.

A prospective study was undertaken to determine the cardiovascular response of a continuous alfentanil infusion during abdominal aortic surgery (AAS). Each subject (n = 20) received a beta-blocking drug preoperatively, and was premedicated with oral lorazepam. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and thiopentone 3 mg.kg-1, and was maintained with a variable rate infusion of alfentanil and 66 per cent nitrous oxide in oxygen. During the infusion, boluses of alfentanil, 7.5 micrograms.kg-1, were administered to maintain heart rate and blood pressure within 20 per cent of awake baseline values. Haemodynamic stability during surgery was achieved with infusion rates varying between 0.5 and 2.5 micrograms.kg-1, which resulted in mean alfentanil serum concentrations ranging from 186 +/- 53 to 315 +/- 98 ng.ml-1. The mean cumulative alfentanil dose was 15.4 +/- 6.2 mg.patient-1 for surgery which lasted an average of 141 +/- 41 min. Throughout surgery, no patient required inhalational anaesthetic agents or vasoactive drugs. Fifteen of the 20 patients had perioperative Holter monitoring. No myocardial ischaemia was detected during the intraoperative period. However, there was a 33 per cent incidence of myocardial ischaemia on the first postoperative day. There were no myocardial infarcts and no deaths. We conclude that in beta-blocked patients undergoing aortic reconstructive surgery, a variable rate alfentanil infusion administered with 66 per cent nitrous oxide provides anaesthesia characterized by good haemodynamic control without the need for supplemental agents or vasoactive drugs.

Alfentanil↗
PubMed1989

Additivity in the sensitizing effects of nitrous oxide and oxygen.

In earlier work, we proposed that nitrous oxide (N2O) and low concentrations of oxygen (10(-6) less than [O2] less than 10(-4) mol dm-3) share a common sensitizing mechanism. We also proposed that the basis for sensitization by N2O is different from that by high concentrations of oxygen ([O2] greater than 10(-4) mol dm-3). We have now tested these proposals with several Escherichia coli strains using mixtures of O2 and N2O. In the strains that are sensitized by N2O, we found that damage from low concentrations of O2 does not add to that from N2O. In contrast, we did find additivity in the sensitizing effects of N2O and high concentrations of O2. In those E. coli strains that are not sensitized by N2O, the effects of any concentration of O2 are the same in either N2 or N2O. These results are qualitatively the same as those from our previous study with E. coli B/r, and they support our proposals concerning similarities and differences in sensitizing mechanisms of N2O and O2.

Cell Survival↗
PubMed1987

Superoxide removal and radiation protection in bacteria.

Previous work with procaryotic cells has identified one kind of lethal damage from ionizing radiation which occurs only within a specific range of low O2 concentrations, about 10(-6) to 10(-4) M. Within this range, protection can occur in three ways: through the enzymatic decomposition of hydrogen peroxide (H2O2) by added catalase, through the enzymatic degradation of superoxide anion radicals (.O2-) by added superoxide dismutase (SOD), and through scavenging hydroxyl radicals (.OH) by various additives. These results indicate that three radiolytic products, H2O2, .OH, and .O2- (and/or the conjugate acid, the perhydroxyl radical, .HO2) are involved in this single kind of radiation-induced damage. Although the radiolytic productions of H2O2 and .O2- are strongly enhanced in higher O2 concentrations, neither enzyme protects when these air-equilibrated bacteria are irradiated. These experiments address this apparent contradiction and focus on the specific issue of why the addition of SOD protects at low but not at high O2 concentrations. We propose that, at a given O2 concentration, .O2- (and/or .HO2) may either react (with some cellular component?) to cause damage or react (with itself) to form hydrogen peroxide (H2O2). The specific O2 concentration during irradiation would determine the relative rates of these competing reactions and therefore the O2 concentration itself would establish whether or not we will observe damage from .O2-.

Escherichia coli↗
PubMed1987

Radiation sensitization of E. coli B/r by mixtures of oxygen and nitrous oxide.

Oxygen (O2) sensitizes bacterial cells in at least two mechanistically different ways, depending on the specific O2 concentration present during irradiation. Based on previous work from this laboratory, it has been proposed that nitrous oxide (N2O) and low concentrations of O2 share a common mechanism for damage. This mechanism, involving the production of superoxide anion radicals (O2-), is different from that which causes damage at high O2 concentrations. Others, however, have presented evidence that N2O and O2 (usually tested only at high concentrations) act in different ways to sensitize bacterial cells. We have now measured the radiation sensitivity in mixtures of N2O and O2 to observe additivity patterns and to determine if these two agents have any common processes for sensitization. We found that some low O2 concentrations do not increase the response in N2O, although they can have significant sensitizing effects in N2. This lack of additivity is taken as evidence for a common mechanism of damage from N2O and low concentrations of O2. In contrast, damage from high concentrations of O2 is additive to the damage from N2O. The greatest sensitivity, observed with a gas mixture of about 15 per cent O2/85 per cent N2O, is equivalent to the response in 100 per cent N2 plus the maximum amount of damage O2 can cause plus the maximum amount of damage N2O can cause. This additivity is taken as evidence that N2O and high concentrations of O2 sensitize in different ways. Thus, O2 is known to sensitize these bacteria in at least two different ways; one of these is apparently also the way N2O sensitizes.

Drug Synergism↗
PubMed1987

Radiation protection of Escherichia coli B/r by hydroxyl radical scavengers.

We have used Escherichia coli B/r to test the proposal that hydroxyl radicals (.OH) are major contributors to lethal damage when bacteria in equilibrium with air or 100% nitrogen are exposed to ionizing radiation. In addition, we have tested the hypothesis that oxygen sensitizes bacterial cells to radiation by reacting at radical sites previously formed by reactions of .OH. Our results with B/r indicate that the involvement of OH radicals in damage may have been overestimated. We believe that simple .OH removal provides B/r with only a relatively small amount of protection in N2 and air. Although some .OH scavengers can have large protective effects in air, evidence supports the tentative conclusion that these effects are not based on simple .OH removal. If this conclusion is correct, then radiation sensitization by oxygen--at least of this bacterial strain--would be unrelated to reactions of .OH.

Butanols↗
PubMed1986

Radiation sensitization by oxygen of in vitro mammalian cells: is .O-2 involved?

Oxygen is a potent sensitizer of cells exposed to ionizing radiation, and, although the exact chemical mechanisms are not fully understood, some evidence suggests that this sensitization may involve the formation of superoxide anion radicals (.O-2) [F. Lavelle, A. M. Michelson, and L. Dimitrijevic, Biochem. Biophys. Res. Commun. 55, 350-357 (1973); A. Petkau and W. S. Chelack, Int. J. Radiat. Biol. 26, 421-426 (1974); L. W. Oberley, A. L. Lindgren, S. A. Baker, and R. H. Stevens, Radiat. Res. 68, 320-328 (1976)] To test this hypothesis, we compared the sensitivity of Chinese hamster V79 cells irradiated in O2/N2 and O2/N2O gas mixtures with and without the addition of other radical scavenging agents. In these tests, although oxygen was present, be blocked the radiation-induced reactions of O2 which produce .O-2. We found that the total amount of biological damage depends simply on the concentration of O2 that is present; the overall sensitivity is not reduced when .O-2 cannot be formed. Thus radiation sensitization by O2--at least of this cell line--does not require the formation of superoxide anion radicals.

Animals↗
PubMed1983

Reliability of transferrin and leucine aminopeptidase phenotyping in wild meadow voles (Microtus pennsylvanicus).

Replicate plasma samples from wild Microtus pennsylvanicus were typed by gradient polyacrylamide gel electrophoresis for the transferrin and leucine aminopeptidase polymorphisms. Phenotypes remained the same through major seasonal changes in reproductive activity and environmental conditions. Possible explanations for the anomalous phenotypic variation seen in Microtus ochrogaster [McGovern M., and Tracy, C. R. (1981). Oecologia 51:276] are discussed.

Animals↗
PubMed1983

Radiation sensitization of E. coli B/r by nitrous oxide.

E. coli B/r have been used to study radiation sensitization by nitrous oxide (N2O). Cells suspended in Sörensen's phosphate buffer show a large amount of sensitization by N2O (relative to the response in 100% N2). Cells in McIlvaine's phosphate-citric acid buffer, however, show no sensitization by N2O. Sensitization in Sörensen's buffer can be prevented by hydroxyl radical (.OH) removal or by catalase. Chemical assays for the amounts of H2O2 formed under various conditions provide the basis for the conclusion that the high concentration of the citrate ion in McIlvaine's buffer does not allow the build-up of H2O2. Sensitization by N2O requires that both H2O2 and OH radicals be present.

Buffers↗
PubMed1983

Synergistic damage from H2O2 and OH radicals in irradiated cells.

The anoxic sensitization of bacterial spores by added H2O2 has been studied. Two mechanistic pathways for damage from H2O2 were found; one of these requires the presence of OH radicals. For this kind of damage, the relationship between H2O2 and OH appears to be that they are reactants. O-2 (and/or HO2), the product of such a reaction, is likely the agent which actually causes damage. These results with reagent H2O2 are compared with results of experiments in which H2O2 and OH are present as radiolytic products.

Bacillus megaterium↗
PubMed1982

Radiobiology of a differentiating cell system in vitro.

Friend erythroleukaemia cells (FELC) in vitro were used to examine the effects of ionizing radiation on differentiation and proliferation of mammalian cells. Results suggest that X-rays can affect differentiation in two different ways. First, X-rays inactivate the ability of these cells to respond to an external trigger of differentiation, e.g., dimethyl sulphoxide. Second, X-rays themselves trigger a partial differentiation response, in the absence of any other external trigger. The radiation-induced lesions leading to these two end-points are not repaired in split-dose experiments, unlike those lesions which lead to loss of cell proliferative capacity. The profile of soluble FELC proteins, as analysed by isoelectric focusing, was also affected by irradiation. These effects of ionizing radiation on the expression of genetic information in mammalian cells have important implications for radiobiology, particularly at low doses where acute lethal effects are minimal.

Animals↗