摘要:

Abstract—Using the spin trap 5,5‐dimethylpyrroline‐1‐oxide we have demonstrated that the nitrosoamine carcinogen, 1‐nitrosopiperidine, upon incubation with rat liver microsomes and nuclei produces two trapped free radical species. One trapped species is the hydroxyl free radical whereas the other is a free radical of unknown structure of the carcinogen itself. Three other nitrosoamine carcinogens tested, including diethylnitrosoamine, dimethylnitrosoamine and 1‐nitrosopyrroline yielded similar results with the exception that the trapped carcinogen radical differs dependent upon the compound used. Oxygen was required to produce the hydroxyl free radical but its presence decreased the yield of the carcinogen radical. Both cyanide and α‐tocopherol acetate caused a decrease in the yield of the carcinogen free radical. Some heat‐labile inhibitor(s) of radical production was/were present in the cytosol. The amount of radical produced was not proportional to

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07032.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—Dye sensitized photo‐oxidation of various chemical carcinogens including 2‐acetylaminofluorene, benzo(a)pyrene, 9,10‐dimethyl‐1,2‐benzanthracene and 4‐nitroquinoline‐N‐oxide has been studied in the presence and absence of oxygen. Visible light from a filtered 150 W Xe arc was used for photolysis. and carcinogen destruction was monitored spectrophotometrically. The carcinogens were solubilized in aqueous solution within micelles of various lipid‐like surfactants. Photosensitized destruction of carcinogens by several triplet sensitizers has been observed. Enhanced damage in the presence of oxygen is also found. These results are consistent with photochemical oxidative damage to carcinogens being produced in aerated solutions via the sensitizer triplet state, possibly involving singlet oxygen. These manifold reactions are catalysed by micelles which concentrate polycyclic hydrocarbons in the non‐polar environment within the micelles where the exclusion of water probably increases reactive species lifetimes. This model photochemical system mimics the aerobic metabolic activation of chemical carcinogens, which in part is believed to be mediated by various form

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07033.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—The nitrobenzenes, the carcinogens 4‐nitropyridine‐N‐oxide and 4‐nitro‐quinoline‐N‐oxide as well as the nitrofurans, also known to be carcinogenic, have been found to enhance the reaction of ascorbate with oxygen. The reaction results in the oxidation of ascorbate, the production of dehydroascorbate, superoxide radical, peroxide and water. The drugs are not reduced to stable intermediates during the oxidation but are recycled to their original state. The oxygen consumption is partially inhibited by either superoxide dismutase or catalase. If both superoxide dismutase and catalase are included in the reaction mixture, total oxygen consumption was equal to the amount expected for oxidation of ascorbate to dehydroascorbate and reduction of oxygen to water. The oxygen consumption was inhibited by ferricytochrome c. Semiquinones, nitro and hydroxylamine radicals, produced by electron transfer from ascorbate, reduce ferricytochromec.These oxygen reactive radicals are responsible for the stimulation of oxygen utilization and ascorbate oxidation. In addition we have found that Ehrlich cells, containing catalase and superoxide dismutase, inhibit the drug catalyzed oxidation of ascorbate. The presence of cyanide, known to inhibit catalase and superoxide dismutase, abolished the cell effect for most of t

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07034.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—Radiation‐induced covalent binding of labelled carcinogens to DNA has been investigated under a variety of conditions using ultrafiltration or millipore filtration of TCA precipitable complexes. High yields of carcinogen binding at high DNA concentrations are also observed for a variety of small molecules and are not carcinogen‐specific. At high carcinogen concentrations, radiation‐induced unstable electrophilic carcinogenic species are produced, and undergo free‐radical reactions which simulate cellular redox reactions involved in metabolic carcinogen activation, leading to the formation of covalently bound carcinogen adducts to DNA as a potential target macromolecule. The yields of carcinogen‐DNA adducts increase linearly with dose and depend upon carcinogen concentration. The results of scavenger studies indicate that the oxidising species O2‐and OH are the principal activating species. Rate constants for the selective radiation‐induced oxidation reactions of various chemical carcinogens with superoxide have been measured by a competition kinetic method using pulse radiolysis. The relatively long‐lived superoxide radical reacts with carcinogens at a rate which is two orders of magnitude slower than the diffusion‐controlled rate for the hydroxyl radical, thus allowing a measure of O2‐specificity in the presence of competing reac

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07035.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—Hydroxyl radicals ('OH) are scavenged by 1,4‐diazabicyclo[2.2.2]octane (DABCO) at a diffusion‐controlled rate of 1.25 ± 0.1 × 109M‐1s‐1. Unlike other efficient 'OH scavengers which exhibit protection of bacteria against irradiation both in oxic and hypoxic conditions, DABCO has been shown to protectSerratia marcescensand various strains ofEscherichia colionly in oxic conditions.DABCO appears to eliminate a component of the sensitization afforded by oxygen in all strains ofE. colitested. The level of this protection increases from ∼15% in the wild type AB 1157 to ∼100% in therecA uvrAmutant AB 2480. It is suggested that DABCO protects against lethal events that can occur on macromolecules other than DNA such as the cell membrane.Results with added glycerol, as well as work in D2O solution, indicate that DABCO is more likely to be acting by scavenging radicals rather than by quenching1O2. If1O2is a component of the sensitization afforded by oxygen, then it is unlikely to be formed in a hydrophilic environm

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07036.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—We report on autooxidation reactions related to selective cell killingin vivoand present oxygen uptake and EPR data on the molecular nature of these changes, with a note on a reaction used to test for singlet oxygen.Selective obliteration by 6‐hydroxydopamine, 6‐aminodopamine and their congeners of beta‐adrenergic cell receptors and of adrenergic and dopaminergic neuronsin vivoandin vitrohave been reported recently. These effects devolve from autoxidation of the compoundsin situafter appropriate biological concentration, but it is unclear whether cytotoxicity is mediated by the reactive oxygen species themselves or by nucleophilic reactions of the product quinones. Because of the possibility of harnessing these reactions for a generalized “chemical surgery” if the former mechanism is operative, and because many other oxidative damage reactions involving unsaturated lipids of biomembranes seem to share similar autoxidative initiating and chain‐carrying steps, we have studied the autoxidation of ascorbate and other reductants catalyzed by polyhydroxy quinols related to 6‐hydroxydopamine. We find that superoxide anion mediation may or may not be important, depending on redox potentials and reaction kinetics of particular compounds. To the extent that the cellular toxicity of these compounds is oxidative in nature, it is facilitated by—and may depend upon—hydroxyl radical production due to Fenton‐type reactions. Likely Fenton reactantsin vivoare hydrogen peroxide produced from the quinol‐catalyzed autoxidations and non‐heme iron reduced cyclically by superoxide anions from the same autoxidations.Studies using flow systems adapted for EPR at 35 GHz have provided support for some of the reaction mechanisms proposed. In nonaqueous solvents eerie oxidation produced transient free radicals from hydrophobic diphenyl and isobenzo furans, which are often cited as “specific” probes for singlet oxy

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07037.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07038.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—We have studied the effect of oxidant injury on the lymphoblastic transformation and glucose metabolism of human lymphocytes. Lymphocyte cultures were incubated with xanthine oxidase and xanthine, an enzyme system known to generate several highly reactive oxygen compounds. Lymphoblastic transformation to phytohemagglutinin was quantitated by the stimulation of DNA synthesis as indicated by the3H‐thymidine uptake of the cultures at 3 days.The lymphoblastic transformation of cultures incubated with the enzyme system was significantly impaired compared to controls. These cultures also failed to demonstrate the burst of glucose metabolism characteristic of transforming cells. To firmly establish that the effect of the enzyme system on lymphoblastic transformation was related to reactive oxygen molecules, the effect of several scavengers was studied. Cultures supplemented with catalase were almost completely protected against the effect of the enzyme system. In contrast, cultures supplemented with superoxide dismutase, mannitol and azide. scavengers of superoxide, hydroxyl radicals, and singlet oxygen, respectively, were not protected. These data indicate that the functional capacity of human lymphocytes can be impairedin vitroby exposure to hydrogen perox

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07039.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

Abstract—The apparentKmfor O2in the photoreduction of molecular oxygen by spinach class II chloroplasts and photosystem I subchloroplast fragments was determined. In both cases, a value of 2 ∼ 3 μMO2was obtained. The reaction rate constant between O2and P‐430, the primary electron acceptor of PS I, is estimated to be ∼ 1.5 × 107M‐1s‐1and the factors affecting the production of superoxide by the photoreduction of O2in chloroplasts are discussed. Preliminary evidence is presented indicating the occurrence of an azide‐insensitive scavenging system for H2O2in chl

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07040.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1978.tb07041.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY