摘要:

AbstractThe radiobiological oxygen effect can be separated into its biological and chemical components, using time‐resolved or kinetic studies. Rapid mix techniques show that the full oxygen enhancement ratio (OER) for radiation‐induced cell killing is expressed when oxygen is present or admitted 40 ms prior to irradiation. This predominant chemical action of oxygen, including direct and indirect action, is too fast to implicate processes other than those involving free radical species. The two principal hypotheses, “oxygen fixation” and “active oxygen”, are discussed. Pulse radiolysis studies of model systems provide kinetic data to indicate the principal damaging species and radiation targets, the kinetics and sequence of damaging events, and the role of redox processes involving oxygen, oxy‐radicals and radiation modifiers. Complementary steady‐state radiolysis studies enable the nature and extent of the physico‐chemical damage to be quantified. Mechanistic aspects of the radiobiological oxygen effect are inferred fromin vitrostudies of irradiated mammalian cells, comparing the different biological end‐points with specific forms of chemical damage, under a variety of physical, chemical and biological conditions.While this review stresses the role of oxygen in sensitizing the critical cellular target DNA, responsible for the acute biological effect of cell killing, it must be remembered that for cancer and other chronic effects, having a long latent period between radiation exposure and the biological expression of deleterious damage, there may not be an oxygen effect or if there is, it may be quite different in terms of the damaging species, principal radiation targets, and the sequence and kinetics of the damaging events. Although oxygen and oxy‐radicals may be involved in the initiation and development of cancer, their overall roles in influencing the chronic effects of radiation may be complex and dependent upon cellular and multicellular factors, making it difficult to unambiguously elucidat

ISSN:0021-2148    

DOI:10.1002/ijch.198400001

出版商:WILEY‐VCH Verlag    

年代:1984

数据来源: WILEY

摘要:

AbstractThe literature on the reaction of cytochromecwith the radiolytically generated radicals\documentclass{article}\pagestyle{empty}\begin{document}$ {\rm e}_{{\rm eq}}^ -,^. {\rm OH,}^{\rm .} {\rm H,CO}_2^ -,{\rm O}_{\rm 2}^ -,{\rm Br}_{\rm 2}^ - $\end{document}and various organic radicals is reviewed. It would appear that negatively charged radicals, aided by the electric field of cytochromec, react at the exposed haem edge. Uncharged organic radicals also react at this site.\documentclass{article}\pagestyle{empty}\begin{document}$ ^. {\rm H} $\end{document}and\documentclass{article}\pagestyle{empty}\begin{document}$ ^. {\rm OH} $\end{document}are likely to reduce the prosthetic group indirectly by a tunnelling mechanism.

ISSN:0021-2148    

DOI:10.1002/ijch.198400002

出版商:WILEY‐VCH Verlag    

年代:1984

数据来源: WILEY

摘要:

AbstractThe kinetic and mechanistic properties of alkoxy radicals in organic solvents are briefly reviewed. Owing to the scarcity of such data in aqueous solutions and since reactions at the membrane/water interface may be also biologically important, we have studied the reactivity of these radicals in water and the results of our investigations are reported. Alkoxy radicals were generated by photolytic or radiolytic cleavage of peroxide precursors (tert‐butyl hydroperoxide and di‐tert‐butyl peroxide as well as hydroperoxides of polyunsaturated fatty acids). A quantitative correlation between the structure of various substances, in particular phenolic antioxidants, and their activity in inhibiting the alkoxy radical‐induced bleaching of the water‐soluble carotenoid crocin will be discussed. Rate constants forintermolecular reactions oft‐BuO radicals were determined by pulse radiolysis. The diffusion‐controlled reaction with the catechol antioxidant nordihydroguaiaretic acid demonstrates an effective competition with the very rapidintramolecularβ‐fragmentation in water. The results support the view that a considerable amount of alkoxy radicals interact with substrates before they can rearrange

ISSN:0021-2148    

DOI:10.1002/ijch.198400003

出版商:WILEY‐VCH Verlag    

年代:1984

数据来源: WILEY

摘要:

AbstractFormation and reactions of the cumyloxyl radical in aqueous solutions were studied by steady‐state and pulse radiolytic techniques. Cumene hydroperoxide reacts with e−aq(k= 4.4 × 109M−1s−1) to yield the cumyloxyl radical. The spectrum recorded after the pulse indicates formation of a species absorbing at 250 nm. This product was identified as acetophenone, which is formed by the fragmentation of the cumyloxyl radical. By comparison of the pseudo‐first‐order rates of e−aqdecay at 600 nm with the rate of production of acetophenone at 245 nm at increasing concentrations of cumene hydroperoxide, it was possible to derive a rate constant of 1.0 × 107s−1for the cleavage of cumyloxyl to acetophenone and methyl radical. This value is higher than that measured previously in organic solvents (1 × 106s−1), as expected. HPLC analysis of the radiation products acetophenone and cumyl alcohol permitted determination of rate constants for hydrogen abstraction by the cumyloxyl radical, in competition with the fragmentation. The rate constants for H abstraction from i‐PrOH, EtOH, and MeOH by CmO were found to be 9.9 × 106, 3.8 × 106, and 8.5

ISSN:0021-2148    

DOI:10.1002/ijch.198400004

出版商:WILEY‐VCH Verlag    

年代:1984

数据来源: WILEY

摘要:

AbstractThe problem of using OH scavengers, with special emphasis on biological systems, is discussed. The problems arising from inhomogeneity and from possible large gradients in scavenger concentrations between the cell and media, or between different parts of the cell, are analysed, and their implications on scavenging efficiency are examined. The possible reactions of secondary radicals and their effect on scavenging and even on possible sensitization are described. The limitations of the usage of OH scavengers in biological systems are discussed.

ISSN:0021-2148    

DOI:10.1002/ijch.198400005

出版商:WILEY‐VCH Verlag    

年代:1984

数据来源: WILEY

摘要:

AbstractKinetic and product studies of liquid phase autoxidations in the presence of high concentrations of alkyl hydroperoxides have enabled absolute propagation and termination rate constants for alkylperoxyls to be measured. A large number of rateconstants and activation parameters have been accumulated over the past few years bythis technique and the highlights of this work are presented in this review.

ISSN:0021-2148    

DOI:10.1002/ijch.198400006

出版商:WILEY‐VCH Verlag    

年代:1984

数据来源: WILEY

摘要:

AbstractA comprehensive reaction schema for oxidative cytotoxicity is presented, integrating known chemical mechanisms of oxygen radical reactions and observed pathophysiology. The key features of the schema are the coupling of (1) redox cycling of autoxidizable substrates to form the equilibrium pair of superoxide anion (O−2)/and its conjugate acid, perhydroxyl radical (HO2); (2) hydrogen peroxide (H2O2) generation via O−2dismutation; (3) catalytic redox cycling of metals reducing H2O2to reactive hydroxyl radicals (OH); (4) direct reaction of OH with target molecules, including critical cell macromolecules and polyunsaturated lipids in membranes; (5) transfer of oxidative potential from initial to distant sites via H2O2and O−2/HO2diffusion, lipid free radical chain peroxidations in membranes, and migration of non‐radical lipid oxidation products; and (6) cytotoxic damage at those distant sites mediated by reaction of lipid radical species and other lipid oxidation products with critical target molecules (proteins, DNA, etc.). Although there is a broad consensus of agreement within the cognizant research community concerning many aspects of this schema, there exists considerable controversy and/or misconception about several important issues. In this paper critical analyses of four presently controversial points are put forth. (1) The question of metal‐dependency of Fenton generation of OH is considered first and data are presented to show that previous observations of apparent H2O2decomposition by various semiquinone radicals most likely resulted from trace metal contamination. (2) The strong electrophile from H2O2reduction has sometimes been ascribed to a non‐free “crypto‐hydroxyl” radical because of failure of traditional scavengers to inhibit its reactions in the expected ways or it has been ascribed to iron‐oxy complexes based on similar “atypical” scavenger patterns plus requirements for preformed ferric iron. The behavior of these species in multiphasic, inhomogeneous systems, which is alleged to be inconsistent with that characteristic of OH, is reconciled with the competitive kinetics expected of OH in three situations: (a) compartmentalization at the cellular level (i.e., in vesicles or their membranes) which prevents access of scavengers to the sites of OH generation, (b) site‐specificity at the molecular level (OH reaction occurring within a few Angstroms of specific metal‐binding sites on macromolecules or in/on membranes), and (c) reactivity of secondary radicals formed by the “scavenging” of OH. (3) The significance of lipids in propagating oxidative damage from the initiation sites of lipid peroxidation to distant sensitive target molecules (proteins and nucleic acids) is discussed, along with the capability of O−2and H2O2to serve similar roles in propagating damage from the sites of autoxidation. (4) Finally, some common misinterpretations regarding “scavengers” and inhibitors of oxygen radical reactions from both chemical and metabolic/physiological standpoints are considered in the context of

ISSN:0021-2148    

DOI:10.1002/ijch.198400007

出版商:WILEY‐VCH Verlag    

年代:1984

数据来源: WILEY

ISSN:0021-2148    

DOI:10.1002/ijch.198400008

出版商:WILEY‐VCH Verlag    

年代:1984

数据来源: WILEY