The role of free radicals in asbestos-induced diseases.

Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases ☆

This review presents and evaluates evidence relevant to the mechanisms of metal carcinogenicity with special emphasis on the emerging hypothesis of the oxidative nature of metals' effect on DNA. The carcinogenic transition metals are capable of in vivo binding with the cell nucleus and causing promutagenic damage that includes DNA base modifications, inter- and intramolecular crosslinking of DNA and proteins, DNA strand breaks, rearrangements, and depurination. The chemistry of that damage and the resulting mutations observed in vitro and in metal-induced tumors are both characteristic for oxidative attack on DNA. The underlying mechanism involves various kinds of active oxygen and other radical species arising from metal-catalyzed redox reactions of O2, H2O2, lipid peroxides, and others, with certain amino acids, peptides, and proteins. Other metal-mediated pathogenic effects, such as enhancement of lipid peroxidation, stimulation of inflammation, inhibition of cellular antioxidant defenses, and inhibiti...

Possible Role of Oxidative Damage in Metal-Induced Carcinogenesis

Oxygen free radicals and their metabolites, collectively described as reactive oxygen species (ROS), have been implicated in the pathogenesis of many diseases. The pulmonary system is particularly vulnerable to ROS-induced injury because of its continuous exposure to toxic pollutants from a wide variety of sources in the ambient air. Additionally, lungs are exposed systemically to ROS generated from xenobiotic compounds and endogenous sources. This review describes the sources of endogenous and exogenous ROS generation in the lung. Special emphasis is given to major sources of ROS in occupational and environmental exposures to asbestos, crystalline silica, coal, chromium, herbicides, bleomycin, and cigarette smoke. ROS-induced lung injury at different target levels may contribute to similar patterns of cell injury and alterations at the molecular level by initiation, propagation, and autocatalytic chain reactions. Intracellular signalling, activation and inactivation of enzymes, stimulation, secretion, and release of proinflammatory cytokines, chemokines, and nuclear factor activation and alterations are also common events. Understanding the interactions of these intricate mechanistic events is important in the prevention and amelioration of lung injury that results from acute and chronic exposures to toxins in ambient air.

The role of oxygen free radicals in occupational and environmental lung diseases.

Quantitative estimates of the risk of lung cancer or mesothelioma in humans from asbestos exposure made by the US Environmental Protection Agency (EPA) make use of estimates of potency factors based on phase-contrast microscopy (PCM) and obtained from cohorts exposed to asbestos in different occupational environments These potency factors exhibit substantial variability The most likely reasons for this variability appear to be differences among environments in fiber size and mineralogy not accounted for by PCM In this article, the US Environmental Protection Agency (EPA) models for asbestos-related lung cancer and mesothelioma are expanded to allow the potency of fibers to depend upon their mineralogical types and sizes This is accomplished by positing exposure metrics composed of nonoverlapping fiber categories and assigning each category its own unique potency These category-specific potencies are estimated in a meta-analysis that fits the expanded models to potencies for lung cancer (KL's) or mesothelioma (KM's) based on PCM that were calculated for multiple epidemiological studies in our previous paper (Berman and Crump, 2008) Epidemiological study-specific estimates of exposures to fibers in the different fiber size categories of an exposure metric are estimated using distributions for fiber size based on transmission electron microscopy (TEM) obtained from the literature and matched to the individual epidemiological studies The fraction of total asbestos exposure in a given environment respectively represented by chrysotile and amphibole asbestos is also estimated from information in the literature for that environment Adequate information was found to allow KL's from 15 epidemiological studies and KM's from 11 studies to be included in the meta-analysis Since the range of exposure metrics that could be considered was severely restricted by limitations in the published TEM fiber size distributions, it was decided to focus attention on four exposure metrics distinguished by fiber width: "all widths," widths > 02 micro m, widths 10 microm) amphibole fibers; rpc, the potency of pure chrysotile (uncontaminated by amphibole) relative to amphibole asbestos; and rps, the potency of shorter fibers (5 microm 02 microm with both rps and rpc fixed at 1 (which is nominally equivalent to the traditional PCM metric), the "all widths" and widths 02 microm metric for mesothelioma), the hypothesis that these shorter fibers were nonpotent could not be rejected for any of these metrics Expansion of these metrics to include a category for fibers with lengths < 5 microm did not find any consistent evidence for any potency of these shortest fibers for either lung cancer or mesothelioma Despite the substantial improvements in fit over that provided by the traditional use of PCM, neither the "all widths" nor the widths < 04 microm metrics (or any of the other metrics evaluated) completely resolve the differences in potency factors estimated in different occupational studies Unresolved in particular is the discrepancy in potency factors for lung cancer from Quebec chrysotile miners and workers at the Charleston, SC, textile mill, which mainly processed chrysotile from Quebec A leading hypothesis for this discrepancy is limitations in the fiber size distributions available for this analysis Dement et al (2007) recently analyzed by TEM archived air samples from the South Carolina plant to determine a detailed distribution of fiber lengths up to lengths of 40 microm and greater If similar data become available for Quebec, perhaps these two size distributions can be used to eliminate the discrepancy between these two studies

https://www.tandfonline.com/doi/pdf/10.1080/10408440802273156

A Meta-Analysis of Asbestos-Related Cancer Risk That Addresses Fiber Size and Mineral Type

According to certain hypotheses, the production of oxygen radicals within the biological medium (the phenomenon of oxidative stress) may play an important role in fibrosis and in certain steps of carcinogenesis. The mineral fibres of various materials are capable of participating in this phenomenon, owing to the reducing nature of their surface activity, so that OH. radicals can be produced from oxygen in 3 steps. The surface activity of inorganic materials which are insoluble or only very slightly soluble is due to the presence of electron donor active sites, generally linked to Fe2+ ions found in the neighbourhood of the surface. In biological systems, these sites may emerge on the surface as a result of the partial dissolution of the particle, the action of a biological reducing agent, the phenomenon of deposition on the surfaces or cation exchange. We have explored the reducing properties of the surfaces of a certain number of mineral fibres, in aqueous buffer medium, by electron paramagnetic resonance (EPR) measurement of the adduct with the radical-trapping agent 5,5'-dimethyl-l-pyrrolidine-N-oxide (DMPO), produced from the radicals initially formed (OH. or R.). We have found certain fibres to be highly effective in producing radicals from dissolved oxygen (Canadian chrysotile, nemalite, freshly ground amphiboles) while others have little effect. The reducing activity of certain fibres may be markedly increased by prior treatment in the presence of a ferrous salt (as in the case of erionite) or by the addition of glutathione to the reaction medium (as in the case of UICC crocidolite). It is suggested that the carcinogenic activity of certain inorganic materials at the pulmonary level is the result of their surface reducing properties. These reducing properties may either be present at the time of inhalation or acquired in the biological medium. This hypothesis is not in conflict with the observation of the role of the dimensional characteristics of fibres in mesothelioma.

Production of oxygen radicals by the reduction of oxygen arising from the surface activity of mineral fibres.

The deleterious effects of radicals in biological systems are now admitted. The aim of the present work was to study the reduction of oxygen and hydrogen peroxide (H2O2) into hydroxyl radicals by selected iron compounds in a phosphate buffered solution. Radical detection has been carried out by electron spin resonance spectroscopy (ESR) with “spin trapping”; (5,5‐dimethyl‐1‐pyrroline N‐oxide, DMPO). The following minerals have been used: goethite (FeOOH a), akaganeite (FeOOH β), hematite Fe2O3α), magnetite (Fe3O4), siderite (FeCO3), and crocidolite fibres (Na2Fe3Si8O22(OH)2). Crocidolite and siderite reduced O2 into OH∗. Catalase inhibited this reduction. The reduction occurs at the mineral surface. When H2O2 was added to the buffer solution, goethite was inactive, akaganeite, magnetite, crocidolite and hematite were active and siderite was very active. These reactions could play a role in the mechanisms of toxic injury caused by some solid iron compounds.

Production of hydroxyl radicals by iron solid compounds

Studies on surface properties of asbestos. IV. Catalytic role of asbestos in fluorene oxidation.

A mechanistic study of the carcinogenicity induced by inorganic fibrous dusts should include research on the possible intervention of redox sites on the surface of these materials when immersed in an aerated aqueous medium (see the general paper by H. Pezerat, this volume). It can be shown that electrophilic species may be produced, by reaction of molecular oxygen with reducing surface sites (SR), on inorganic particles according to the general scheme below:

$$ {{S}_{R}}\xrightarrow[{{H}_{2}}O]{{{O}_{2}}}{{O}^{*}} $$

The Role of Iron in the Redox Surface Activity of Fibers. Relation to Carcinogenicity

While it is true that fiber morphology increases, amplifies, the carcinogenic activity of an insoluble inorganic particle, the mechanism of genotoxicity will be, very probably, the same as the one observed with organic materials, that is an attack of the genome by electrophilic entities.

R. Zalma

Papers

Production of oxygen radicals by the reduction of oxygen arising from the surface activity of mineral fibres.

Production of hydroxyl radicals by iron solid compounds

Studies on surface properties of asbestos. IV. Catalytic role of asbestos in fluorene oxidation.

The Role of Iron in the Redox Surface Activity of Fibers. Relation to Carcinogenicity

Production of Radicals Arising from Surface Activity of Fibrous Minerals