PubMed Health⌕ Search

Biomedical subjects

W A Pryor

Publications and source records attributed to W A Pryor.

At least 145 records · Page 8Linked to original sources
PubMed1986

Hydroperoxide-induced radical production in liver mitochondria.

When isolated rat liver mitochondria are treated with tert-butyl hydroperoxide in the presence of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide, a six-line ESR signal is observed with parameters characteristic of a carbon-centered radical. The radical is shown to be CH3. using 2-methyl-2-nitrosopropane as the spin trap. Inhibition of radical production by EDTA and N-ethylmaleimide provides evidence for participation by metals and reduced sulfhydryl groups in the radical-generating reaction. It is proposed that radicals are formed through the reaction between a reducing agent, a metal and the hydroperoxide.

Animals↗
PubMed1986

Cancer and free radicals.

It is now clear that free radical intermediates often are involved in the activation of many types of procarcinogens and promutagens to their active forms as well as in the binding of these activated species to DNA. In this chapter, a general introduction to free radical chemistry is presented, with some discussion of radical lifetimes and reactivities. Potential biological targets of radical attack include lipids, proteins, and nucleic acids, and the reactions of all three of these target molecules with radicals are discussed. Finally, the evidence linking free radical reactions with chemical carcinogenesis is reviewed. A mechanistic scheme that divides the mechanisms for activating procarcinogens into 5 types is suggested; of these, 3 types of mechanisms involve free radicals, either in the activation of the carcinogen or in its binding to DNA or both. It also is suggested that a "reverse binding" can occur in which radicals produced on the DNA backbone attack and bond to unactivated substrates, rather than activated substrates (such as radicals) attacking unactivated DNA. It is known that systems that produce superoxide can lead to the production of hydroxyl radicals and that these HO. radicals form radical sites on DNA; thus, reverse binding could occur when any species that can add to a free radical is in the vicinity of the radical-damaged DNA.

Animals↗
PubMed1986

The inactivation of alpha-1-proteinase inhibitor by gas-phase cigarette smoke: protection by antioxidants and reducing species.

The abilities of a number of compounds of biological interest to protect alpha-1-proteinase inhibitor (alPI) against the loss of elastase inhibitory capacity (EIC) resulting from exposure to gas-phase cigarette smoke have been tested. We have identified several species that protect AlPI. Amino acids prevent the loss of EIC in a manner that correlates with their pK alpha-values; only the unprotonated amine provides protection. Catalase partially prevents the loss of EIC, suggesting that hydrogen peroxide produced from the reduction of oxygen in cigarette smoke extracts is responsible for at least some of the smoke-induced inactivation. The best protection against smoke-induced loss of EIC was provided by two biologically important antioxidant species: glutathione and ascorbic acid. Both species provide almost complete protection to alPI under the experimental conditions used. The nature of species that protect AlPI against the inactivation caused by exposure to gas-phase smoke provides clues upon which speculations about the mechanism of this inactivation may be based. The identification of protective species could lead to the development of compounds that smokers could take (for example, vitamin C) that would protect their lung tissue against the oxidative damage caused by cigarette smoke.

Amines↗
PubMed1985

A comparison of the rates of ozonation of biological antioxidants and oleate and linoleate esters.

The rates of reaction with ozone of some biological antioxidants and simple polyunsaturated fatty acids (PUFA) have been measured in water or in aqueous micellar solutions. At pH 7.0 the rate constants are ca. 10(6) M-1 sec-1 for urate, alpha-tocopherol, and PUFA, and 6 X 10(7) M-1 sec-1 for ascorbate. When ozone-containing air is breathed, ascorbate in the lung may undergo direct ozonation. However, alpha-tocopherol is probably spared direct reaction with ozone because it doesn't effectively compete with PUFA in pulmonary membranes; rather, tocopherol is used to scavenge radicals produced from the ozone-PUFA reaction.

Antioxidants↗
PubMed1985

Cigarette tar causes single-strand breaks in DNA.

The results of this study demonstrate, for the first time, that cigarette tar causes DNA damage. Incubation in vitro of phage PM2 DNA with aqueous extracts of cigarette tar results in the introduction of DNA single-strand breaks. The effects of protective enzymes and radical scavengers indicate the involvement of active oxygen species. Although the semiquinone components of tar reduce dioxygen forming superoxide radicals and hydrogen peroxide, our results suggest that hydroxyl radicals formed via metal catalyzed decomposition of hydrogen peroxide are ultimately responsible for the DNA lesions. Our results also suggest that the metals in tar are reduced by the semiquinone components of tar and by superoxide at comparable rates.

Bacteriophages↗
PubMed1985

The metal-mediated formation of hydroxyl radical by aqueous extracts of cigarette tar.

Aqueous extracts of cigarette tar produce hydroxyl radicals that are spin trapped by 5,5-dimethyl-1-pyrroline-N-oxide. The addition of catalase almost completely inhibits and superoxide dismutase partially inhibits spin adduct formation. The addition of ethylenediamine tetraacetic acid greatly increases the amount of hydroxyl radical adduct observed; in contrast, diethylenetriamine pentaacetic acid causes complete inhibition of spin adduct formation. We suggest that the hydroxyl radical arises from the metal-mediated decomposition of hydrogen peroxide, and that hydrogen peroxide is formed from the reduction of dioxygen by the semiquinones present in the cigarette tar.

Catalase↗
PubMed1985

Toxicity of polycyclic aromatic hydrocarbons. I. Effect of phenanthrene, pyrene, and their ozonized products on blood chemistry in rats.

Male Sprague-Dawley rats were treated with a single ip injection of physiological saline (3.0 ml/kg), dimethyl sulfoxide (DMSO, 3.0 ml/kg), phenanthrene (150 mg/kg), ozonized products of phenanthrene (150 mg/kg), pyrene (150 mg/kg), or ozonized products of pyrene (150 mg/kg). Phenanthrene, pyrene, and their ozonized products were dissolved in DMSO (50 mg/ml). Serum aspartate aminotransferase (AST) activity was increased significantly 24 hr after ip administration of DMSO when compared with physiological saline. Phenanthrene produced a significant elevation of serum AST and gamma-glutamyl transpeptidase (GGTP) levels related to physiological saline and DMSO-injected rats 24 hr after injection. However, GGTP levels for groups treated with DMSO or phenanthrene were not significantly increased when compared with saline groups 72 hr after injection. Ozonized products of phenanthrene produced a significant elevation of serum AST, alanine aminotransferase (ALT), GGTP, and bilirubin levels when compared with groups treated with physiological saline, DMSO, and phenanthrene 24 or 72 hr after injections. The ozonized products of phenanthrene also produced significant elevation of serum creatinine levels compared with physiological saline, DMSO, and phenanthrene groups at 24 hr after treatment and of blood urea nitrogen (BUN) levels at 24 and 72 hr. Although pyrene caused a small but significant increase in the serum AST and bilirubin levels 24 hr after treatment, no significant change in the serum AST, ALT, GGTP, BUN, and creatine levels were observed with the ozonized products of pyrene at 24 or 72 hr. This study demonstrates significant alterations in serum chemistry induced by reaction products of ozone with phenanthrene. No such effect was observed when the products of pyrene ozonation were administered. Although the ozonation products of pyrene were not toxic under the conditions of this study, phenanthrene products were more hepatotoxic than was phenanthrene itself. Nephrotoxicity was also an apparent effect of ozonized phenanthrene. Since ozone-polycyclic aromatic hydrocarbon (PAH) reactions may occur in the atmosphere, these reactions might produce compounds that are more toxic than either ozone or the PAH alone.

Alanine Transaminase↗
PubMed1985

Human alpha-1-proteinase inhibitor is inactivated by exposure to sidestream cigarette smoke.

Direct exposure of human alpha-1-proteinase inhibitor (alpha 1PI) to sidestream cigarette smoke causes an initial, rapid loss of elastase inhibitory capacity followed by a slow, gradual loss of activity as the protein is incubated in the smoke-exposed aqueous buffer solution. The exposure used here gives a total of 40% inactivation using one cigarette. This biphasic pattern of inactivation is similar to the inactivation seen following the direct exposure of alpha 1PI to mainstream smoke. We suggest that although exposures to sidestream smoke by nonsmokers are generally lower than the exposures to mainstream smoke experienced by smokers, sidestream smoke has the potential to produce similar types of damage as mainstream smoke, including emphysema-like damage, and should not be regarded as innocuous.

Blood Proteins↗
PubMed1985

Mechanisms of cigarette smoke toxicity: the inactivation of human alpha-1-proteinase inhibitor by nitric oxide/isoprene mixtures in air.

A mixture of nitric oxide (NO) and isoprene in air has been studied as a model for gas-phase cigarette smoke. We have shown that this model system duplicates many of the properties of cigarette smoke including the inactivation of human alpha-1-proteinase inhibitor (a1PI). In this study, buffered solutions of a1PI were exposed to puffs of air containing 300 ppm NO and 400 ppm isoprene. Bubbling of the NO/air/isoprene gas stream directly through buffered protein solutions causes a1PI to undergo a fast loss of inhibitory capacity. This fast inactivation is not observed when a1PI is exposed to aqueous extracts of the NO/air/isoprene mixture. Both direct exposure and exposure to aqueous extracts, however, cause a1PI to undergo a slow loss of activity that continues for several days as the protein is incubated in the buffer solutions. Gas-phase cigarette smoke has already been shown to cause this same two-phase inactivation of a1PI. The inactivation of a1PI by the model system is dependent on the presence of oxygen in the gas stream, suggesting that the oxidation of nitric oxide to nitrogen dioxide in air is involved in the formation of the inactivating species. The nature of these species remains to be determined; however, small alkoxyl or peroxyl radicals (such as are spin-trappable from gas-phase smoke as well as from the NO/air/isoprene system) do not appear to inactivate a1PI. One possibility is that the inactivating species are metastable compounds formed by radical processes in the gas phase of both cigarette smoke and our model system. Our data suggest that one possible class of species is peroxynitrates.

Blood Proteins↗
PubMed1985

Inactivation of human alpha 1-proteinase inhibitor by cigarette smoke: effect of smoke phase and buffer.

In order to resolve a discrepancy in the literature, we have examined the in vitro inactivation of human alpha 1-proteinase inhibitor by direct exposures either to whole cigarette smoke or to filtered (i.e., gas-phase) smoke. Wyss and coworkers (2) reported that whole smoke does not inactivate the protein, whereas we reported that gas-phase smoke does. We now find that direct exposure to gas-phase cigarette smoke causes a slightly greater inactivation of the protein than does direct exposure to whole cigarette smoke, confirming our earlier suggestion that whole smoke is less oxidizing than is gas-phase smoke. This difference, however, does not explain the dramatic difference between our previous findings and those of Wyss and coworkers (2). The explanation for the discrepancy lies in the nature of the buffers used. Wyss and coworkers used Tris buffer and the use of Tris quenches the inactivation process almost completely. Our experiments used phosphate buffer. We suggest that Tris is an unsuitable buffer for use in experiments that probe the effects of cigarette smoke.

Blood Proteins↗
PubMed1985

Free-radical chemistry of cigarette smoke and its toxicological implications.

Cigarette smoke contains two very different populations of free radicals, one in the tar and one in the gas phase. The tar phase contains several relatively stable free radicals; we have identified the principal radical as a quinone/hydroquinone (Q/QH2) complex held in the tarry matrix. We suggest that this Q/QH2 polymer is an active redox system that is capable of reducing molecular oxygen to produce superoxide, eventually leading to hydrogen peroxide and hydroxyl radicals. In addition, we have shown that the principal radical in tar reacts with DNA in vitro, possibly by covalent binding. The gas phase of cigarette smoke contains small oxygen- and carbon-centered radicals that are much more reactive than are the tar-phase radicals. These gas-phase radicals do not arise in the flame, but rather are produced in a steady state by the oxidation of NO to NO2, which then reacts with reactive species in smoke such as isoprene. We suggest that these radicals and the metastable products derived from these radical reactions may be responsible for the inactivation of alpha 1-proteinase inhibitor by fresh smoke. Cigarette smoke oxidizes thiols to disulfides; we suggest the active oxidants are NO and NO2. The effects of smoke on lipid peroxidation are complex, and this is discussed. We also discuss the toxicological implications for the radicals in smoke in terms of a number of radical-mediated disease processes, including emphysema and cancer.

Blood Proteins↗
PubMed1984

Inactivation of human alpha-1-proteinase inhibitor by gas-phase cigarette smoke.

Direct exposure of human alpha-1-proteinase inhibitor to the gas-phase smoke from one cigarette results in an initial rapid loss of elastase inhibitory capacity, the amount of which is dependent upon the age of the smoke. This short-term inactivation is not seen when the protein is exposed to aqueous extracts of cigarette smoke (as had been done in the past). Both exposure regimens result in a slow inactivation occurring over several days. We suggest that the short-term inactivation may be due to a peroxynitrate (or a similar reactive species) that is formed from radicals in the gas phase but is unstable in aqueous solution.

Humans↗
PubMed1983

The radicals in cigarette tar: their nature and suggested physiological implications.

The paramagnetism of cigarette tar is found to be associated with at least four different types of species. One of the types is responsible for over 80 percent of the total paramagnetism and has a signal intensity that is independent of temperature from 60 to 250 K. This non-Curie-Weiss temperature dependence indicates that the principal paramagnetic species in tar is not an organic monoradical (doublet) species but instead is a donor-acceptor excimer with a paramagnetic excited state and a diamagnetic ground state. Modeling experiments suggest that the excimer consists of quinone (Q) and hydroquinone (QH2) molecules held in a tar matrix. Since such Q-QH2 species are catalysts for the oxidation of hydrocarbons and are very active redox systems, this paramagnetic species may be implicated in the cocarcinogenic properties of tar. Alternatively, since semiquinone radicals are known to bind to DNA, the tar paramagnetic species may be directly involved in the carcinogenic properties of tar.

Benzene↗
PubMed1983

Electron-spin resonance study of mainstream and sidestream cigarette smoke: nature of the free radicals in gas-phase smoke and in cigarette tar.

Radicals in the gas phase of both mainstream and sidestream cigarette smoke have been studied using electron-spin resonance ESR spin-trapping techniques with alpha-phenyl-N-tert-butyl nitrone (PBN) as the spin trap. The principal radicals we trap appear to be alkoxyl radicals. Mainstream and sidestream gas-phase smoke each have about the same concentration of radicals, about 1 X 10(16) radicals per cigarette (or 5 X 10(14) per puff). These radicals are reactive, yet they appear to be remarkably long-lived: they are still spin trapped from gas-phase smoke after more than 5 min. We propose that a steady-state concentration of reactive radicals exists in gas phase cigarette smoke. We suggest that this steady state is produced by the slow oxidation of nitric oxide (present in high concentrations in smoke and relatively unreactive) to the more reactive nitrogen dioxide, followed by the reaction of nitrogen dioxide with reactive organic molecules in smoke (such as olefins and dienes). Preliminary experiments reported here support this hypothesis. Tar from both mainstream and sidestream smoke contains persistent free radicals that exhibit broad, single-line ESR spectra with g values of 2.003. The tar radical can be extracted into tert-butylbenzene and other organic solvents, and we have applied a variety of fractionation procedures to these solutions. Most of the radicals occur in the fractions that contain the phenolic tobacco leaf pigments. Treatment of alcoholic solutions of tar with base generates a new group of radicals that appear to be semiquinone radicals derived from the oxidation of the phenolic and polyphenolic species in tar.

Chemical Phenomena↗
PubMed1982

The role of superoxide in xanthine oxidase-induced autooxidation of linoleic acid.

The effect of hydroxyperoxyoctadecadienoic acid, e.g. 13-hydroperoxy-cis,9,trans-11-octadecadienoic acid, on the autooxidation of linoleic acid induced by superoxide radical was examined in a system containing xanthine oxidase, acetaldehyde, and diethylenetriaminepentaacetic acid dissolved in an aqueous phosphate buffer containing 10% ethanol. The superoxide radical is required for autooxidation, as shown by essentially complete inhibition on the addition of superoxide dismutase. Pure linoleic acid was not readily oxidized, but the addition of lipid hydroperoxide markedly stimulated the autooxidation. Addition of 2.8 microM FeCl3 did not produce an increase in the rate of xanthine oxidase-induced autooxidation. Spontaneous autooxidation, a process slower than xanthine oxidase-induced autooxidation, was detectable on the time scale of these observations but was slower than the xanthine oxidase-induced autooxidation. Initiation of linoleic acid autooxidation is postulated to result from a reaction between superoxide and lipid hydroperoxide. The nature of this reaction is uncertain, but it does not appear to depend on iron catalysis.

Animals↗