Chemical Research in Toxicology

Our medical research library holds 16 studies published in Chemical Research in Toxicology (1997–2026). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 15 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: American Chemical Society
• Published: 1988 to the present, United States
• Language: English
• ISSN: 0893-228X (print), 1520-5010 (electronic)
• Its record in the NLM Catalog

2020s

• Kinetics of H2O2-Induced Hydroxyl Radical Release by Carcinogenic Mineral Fibers Crocidolite, Chrysotile, and Erionite. E. Castellini, A.F. Gualtieri. 2026;39(9):1659-1671. PubMed · Publisher · Free full text

  Abstract

  Hydroxyl radicals (•OH) display cyto- and genotoxicity and the ability to induce oxidative stress and chronic inflammation in vivo. In this work, we have monitored the kinetic profile of •OH radical release from the carcinogenic mineral fibers crocidolite, chrysotile, and erionite at physiological pH (7.4). This was achieved via fluorescence spectroscopy, using coumarin-3-carboxylic acid as a semiquantitative probe. A kinetic model was developed to interpret the data. The formation of •OH radicals is initiated by the binding of hydrogen peroxide (H2O2) to Fe2+ sites on the fibers, leading to oxidation to Fe3+ and release of •OH through the Fenton reaction. •OH release was also detected at acidic pH (4.1) under conditions that mimic the intracellular environment during fiber phagocytosis. Although the experiments were conducted in a simplified chemical system, some hypotheses on the activity of the investigated fibers in the extracellular alveolar environment can be done. The results suggest that •OH generation is governed by a multistep mechanism that depends on the specific crystal-chemical nature of the fiber. At pH 7.4, crocidolite exhibits a radical production process which consists of a transition from a rapid oxidation of pristine surface Fe2+ to a continuous, long-term redox cycling of Fe3+. A similar long-term activity was observed for chrysotile, although masked at longer time scales by probe adsorption. In contrast, erionite, which lacks structural iron, releases •OH at a slower rate but with a long-lasting process, likely driven by the reduction of Fe3+ present in nanoparticulate surface impurities. At long incubation times and also at acidic pH 4.1, the kinetic model and experimental evidence address the overlapping contribution of iron dissolution, indicating that homogeneous Fenton reactions complement the heterogeneous surface activity. These findings highlight distinct, time-dependent oxidative pathways for these mineral fibers, providing deeper insights into their specific biochemical mechanisms.

  © 2026 The Authors. Published by American Chemical Society.

• The Potential Contribution of Hexavalent Chromium to the Carcinogenicity of Chrysotile Asbestos. M. Walter, W.D.C. Schenkeveld, M. Tomatis, et al. 2022;35(12):2335-2347. PubMed · Publisher · Free full text

  Abstract

  Chrysotile asbestos is a carcinogenic mineral that has abundantly been used in industrial and consumer applications. The carcinogenicity of the fibers is partly governed by reactive Fe surface sites that catalyze the generation of highly toxic hydroxyl radicals (HO•) from extracellular hydrogen peroxide (H2O2). Chrysotile also contains Cr, typically in the low mass permille range. In this study, we examined the leaching of Cr from fibers at the physiological lung pH of 7.4 in the presence and absence of H2O2. Furthermore, we investigated the potential of cells from typical asbestos-burdened tissues and cancers to take up Cr leached from chrysotile in PCR expression, immunoblot, and cellular Cr uptake experiments. Finally, the contribution of Cr to fiber-mediated H2O2 decomposition and HO• generation was studied. Chromium readily dissolved from chrysotile fibers in its genotoxic and carcinogenic hexavalent redox state upon oxidation by H2O2. Lung epithelial, mesothelial, lung carcinoma, and mesothelioma cells expressed membrane-bound Cr(VI) transporters and accumulated Cr up to 10-fold relative to the Cr(VI) concentration in the spiked medium. Conversely, anion transporter inhibitors decreased cellular Cr(VI) uptake up to 45-fold. Finally, chromium associated with chrysotile neither decomposed H2O2 nor contributed to fiber-mediated HO• generation. Altogether, our results support the hypothesis that Cr may leach from inhaled chrysotile in its hexavalent state and subsequently accumulate in cells of typically asbestos-burdened tissues, which could contribute to the carcinogenicity of chrysotile fibers. However, unlike Fe, Cr did not significantly contribute to the adverse radical production of chrysotile.

• Asbestos and Zeolites: from A to Z via a Common Ion. G. Reid, S. Klebe, N. van Zandwijk, et al. 2021;34(4):936-951. Review PubMed · Publisher

  Abstract

  Asbestos and zeolites are silicate-based minerals, linked inextricably via paradoxical similarities and differences which have emanated from different geological epochs. Both have been employed in the service of humanity through millennia: asbestos, for its "inextinguishable" quality of being an insulator against heat and fire; zeolite, a "boiling stone" with its volcanic and marine sedimentary rock origins, for its propensity to adsorb water and remove metals and toxins. Serious adverse health effects observed in asbestos miners as long ago as the 1st Century AD did not halt the rising popularity of asbestos. As the miracle material of the 1900s, asbestos production and consumption exploded, culminating in its ubiquity in ships, vehicles, homes, commercial buildings, and over 3000 different industrial and household products. Through the 1940s and 1950s, epidemiological studies concluded that asbestos was a likely cause of asbestosis, lung cancer, and malignant mesothelioma, and it is now banned in many but far from all countries. The long latency between exposure to asbestos and the occurrence of cancer has obscured the deadly consequences of asbestos exposure for centuries. Even today, a considerable part of the world population is insufficiently aware of the dangers of asbestos, and millions of tons of this carcinogen continue to be mined and used worldwide. Zeolites, both natural and synthetic, are microporous aluminosilicate minerals commonly used in a myriad of processes, in the petrochemical industry, in domestic appliances and cleaning agents, as commercial adsorbents and exchangers for toxins and pollutants, and as catalysts. Zeolites are found in agriculture, veterinary science, and human health. More recently, new materials such as carbon nanotubes are being employed in materials requiring durability and thermal and electrical conductivity, yet nanotubes are now joining the ranks of more established particulates such as asbestos and silica, in causing human disease. In this review, we compare and contrast the similarities and differences of these two groups of silicate minerals and their waxing and waning use in the employ of humanity.

• Correction to Asbestos and Zeolites: from A to Z via a Common Ion. G. Reid, S. Klebe, N. van Zandwijk, et al. 2021;34(6):1694. PubMed · Publisher

2010s

• Carbon Nanotube- and Asbestos-Induced DNA and RNA Methylation Changes in Bronchial Epithelial Cells. E. Emerce, M. Ghosh, D. Öner, et al. 2019;32(5):850-860. PubMed · Publisher

  Abstract

  Carbon nanotubes (CNTs) are nanoscale tube-shaped carbon materials used in many industrial areas. Their fiber shape has caused concerns about their toxicity given their structural similarity with asbestos. The aim here was to elucidate the effect of CNTs and asbestos exposure on global DNA and RNA methylation and the methylation of genes associated with cell cycle, inflammation, and DNA damage processes in human lung cells. Human bronchial epithelial cells (16HBE14o-) were exposed for 24 h to 25 and 100 μg/mL CNTs (single-walled CNTs [SWCNTs] and multiwalled CNTs [MWCNTs]) and 2.5 μg/mL asbestos (chrysotile, amosite, and crocidolite). Global DNA and RNA (hydroxy)methylation to cytosines was measured by a validated liquid chromatography tandem-mass spectrometry method. Global RNA methylation to adenines was measured by a colorimetric ELISA-like assay. Gene-specific DNA methylation status at certain cytosine-phosphate-guanine (CpG) sites of cyclin-dependent kinase inhibitor 1A ( CDKN1A), serine/threonine kinase ( ATM), and TNF receptor-associated factor 2 ( TRAF2) were analyzed by using bisulfite pyrosequencing technology. Only MWCNT-exposed cells showed significant global DNA hypomethylation of cytosine and global RNA hypomethylation of adenosine. SWCNT, MWCNT, and amosite exposure decreased DNA methylation of CDKN1A. ATM methylation was affected by chrysotile, SWCNT, and MWCNT. However, SWCNT exposure led to DNA hypermethylation of TRAF2. These findings contribute to further understanding of the effect of CNTs on different carcinogenic pathways.

• Structure Model and Toxicity of the Product of Biodissolution of Chrysotile Asbestos in the Lungs. A.F. Gualtieri, G. Lusvardi, A. Pedone, et al. 2019;32(10):2063-2077. PubMed · Publisher

  Abstract

  Asbestos is a commercial term indicating six natural silicates with asbestiform crystal habit. Of these, five are double-chain silicates (amphibole) and one is a layer silicate (serpentine asbestos or chrysotile). Although all species are classified as human carcinogens, their degree of toxicity is still a matter of debate. Amphibole asbestos species are biopersistent in the human lungs and exert their chronic toxic action for decades, whereas chrysotile is not biopersistent and transforms into an amorphous silica structure prone to chemical/physical clearance when exposed to the acidic environment created by the alveolar macrophages. There is evidence in the literature of the toxicity of chrysotile, but its limited biopersistence is thought to explain the difference in toxicity with respect to amphibole asbestos. To date, no comprehensive model describing the toxic action of chrysotile in the lungs is available, as the structure and toxic action of the product formed by the biodissolution of chrysotile are unknown. This work is aimed at fulfilling this gap and explaining the toxic action in terms of structural, chemical, and physical properties. We show that chrysotile's fibrous structure induces cellular damage, mainly through physical interactions. Based on our previous work and novel findings, we propose the following toxicity model: inhaled chrysotile fibers exert their toxicity in the alveolar space by physical and biochemical action. The fibers are soon leached by the intracellular acid environment into a product with residual toxicity, and the dissolution process liberates toxic metals in the intracellular and extracellular environment.

• Asbestos: Modern Insights for Toxicology in the Era of Engineered Nanomaterials. E. Felley-Bosco, M. MacFarlane. 2018;31(10):994-1008. PubMed · Publisher

  Abstract

  Asbestos fibers are naturally occurring silicates that have been extensively used in the past, including house construction, but because of their toxicity, their use has been banned in 63 countries. Despite this, more than one million metric tons of asbestos are still consumed annually in countries where asbestos use has not been banned. Asbestos-related disease incidence is still increasing in several countries, including those countries that banned the use of asbestos more than 30 years ago. We highlight here recent knowledge obtained in experimental models about the mechanisms leading to tumor development following asbestos exposure, including genetic and epigenetic changes. Importantly, the landscape of alterations observed experimentally in tumor samples is consistent with alterations observed in clinical tumor samples; therefore, studies performed on early/precancer stages should help inform secondary prevention, which remains crucial in the absence of an efficient primary prevention. Knowledge gathered on asbestos should also help address future challenges, especially in view of the increased production of new materials that may behave similarly to asbestos fibers.

• Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled Carbon Nanotubes. D. Liao, Q. Wang, J. He, et al. 2018;31(10):1025-1031. PubMed · Publisher

  Abstract

  Translocation of multiwalled carbon nanotubes (MWCNTs) from the lung to the pleural cavity, deposition of the fibers in the pleural tissue, induction of pleural fibrosis, and mesothelial proliferation have been found in rodents administered MWCNTs by different pulmonary exposure methods. However, whether the translocation and deposition and the subsequent pleural inflammation are associated with the pleural lesions is unclear. In the present study, male F344 rats were given 250 μg of two types of MWCNTs, with crocidolite as a positive control, 2 times/week for 4 weeks by intratracheal spraying. At 24 h and at 3 months after the last spraying, the rats were sacrificed for histological examination of the lung and chest wall; pleural cavity lavage was also collected at sacrifice for observation of pleural inflammatory reactions. The results indicated that intratracheally sprayed MWCNTs, like crocidolite fibers, translocated into the pleural cavity, deposited in the pleura, and induced persistent infiltration of immune cells into the pleural cavity, persistent pleural fibrosis, and mesothelial proliferation. The number of MWCNT fibers detected in the pleural cavity lavage was parallel to the number of infiltrating immune cells, which were mainly composed of macrophages. Analysis of cytokines in the fluids of the pleural cavity lavages by suspension array indicated that levels of IL-2, IL-18, and IP-10 were significantly increased both at 24 h and at 3 months after the last spraying. In vitro proliferation assays revealed that a mixture of IL-2, IL-18, and IP-10, but not any of these cytokines alone, promoted cell proliferation of human fibroblasts and mesothelial cells. These results suggest that translocated and deposited MWCNTs induce subsequent pleural inflammation and that increased IL-2, IL-18, and IP-10 synergistically promote the development of pleural fibrosis and mesothelial proliferation.

• Surface reactivity and cell responses to chrysotile asbestos nanofibers. F. Turci, M. Colonna, M. Tomatis, et al. 2012;25(4):884-94. PubMed · Publisher

  Abstract

  High aspect-ratio nanomaterials (HARNs) have recently attracted great attention from nanotoxicologists because of their similarity to asbestos. However, the actual risk associated with the exposure to nanosized asbestos, which escapes most regulations worldwide, is still unknown. Nanometric fibers of chrysotile asbestos have been prepared from two natural sources to investigate whether nanosize may modulate asbestos toxicity and gain insight on the hazard posed by naturally occurring asbestos, which may be defined as HARNs because of their dimensions. Power ultrasound was used to obtain nanofibers from two different chrysotile specimens, one from the dismissed asbestos mine in Balangero (Italian Western Alps) and the other from a serpentine outcrop in the Italian Central Alps. Electron microscopy, X-ray diffraction, and fluorescence spectroscopy revealed that the procedure does not affect mineralogical and chemical composition. Surface reactions related to oxidative stress, free radical generation, bioavailability of iron, and antioxidant depletion, revealed a consistent reduction in reactivity upon reduction in size. When tested on A549 human epithelial cells, the pristine but not the nanosized fibers proved cytotoxic (LDH release), induced NO production, and caused lipid peroxidation. However, nanofibers still induced some toxicity relevant oxidative stress activity (ROS production) in a dose-dependent fashion. The reduction in length and a lack of poorly coordinated bioavailable iron in nanochrysotile may explain this behavior. The present study provides a one-step procedure for the preparation of a homogeneous batch of natural asbestos nanofibers and shows how a well-known toxic material might not necessarily become more toxic than its micrometric counterpart when reduced to the nanoscale.

2000s

• Structural defects play a major role in the acute lung toxicity of multiwall carbon nanotubes: physicochemical aspects. I. Fenoglio, G. Greco, M. Tomatis, et al. 2008;21(9):1690-7. PubMed · Publisher

  Abstract

  Carbon nanotubes (CNT) have been reported to elicit toxic responses in vitro and in vivo, ascribed so far to metal contamination, CNT length, degree of oxidation, or extent of hydrophilicity. To examine how structural properties may modulate the toxicity of CNT, one preparation of multiwall CNT has been modified (i) by grinding (introducing structural defects) and subsequently heating either in a vacuum at 600 degrees C (causing reduction of oxygenated carbon functionalities and reduction of metallic oxides) or in an inert atmosphere at 2400 degrees C (causing elimination of metals and annealing of defects) and (ii) by heating at 2400 degrees C in an inert atmosphere and subsequently grinding the thermally treated CNT (introducing defects in a metal-deprived carbon framework). The presence of framework and surface defects, metals, and oxygenated functionalities was monitored by means of a set of techniques, including micro-Raman spectroscopy, adsorption calorimetry, X-ray photoelectron spectroscopy, inductively coupled plasma mass spectrometry, and atomic emission spectroscopy. Contrary to traditional toxicants, such as asbestos, CNT may quench rather than generate oxygenated free radicals. The potential of the modified CNT to scavenge hydroxyl radicals was thus evaluated by means of electron spin resonance spectroscopy (spin trapping). The original ground material exhibited a scavenging activity toward hydroxyl radicals, which was eliminated by heating at 2400 degrees C but restored upon grinding. This scavenging activity, related to the presence of defects, appears to go paired with the genotoxic and inflammatory potential of CNT reported in the companion paper. Thus, defects may be one of the major factors governing the toxic potential of CNT.

• Genotoxic mechanisms of asbestos fibers: role of extranuclear targets. A. Xu, X. Huang, Y.C. Lien, et al. 2007;20(5):724-33. PubMed · Publisher

  Abstract

  Asbestos fibers are carcinogenic to both humans and experimental animals. The continued discoveries of exposure routes whereby the general public is exposed to asbestos suggest a long-term, low-dose exposure for a large number of people. However, the mechanisms by which asbestos induces malignancy are not entirely understood. In previous studies, we have shown that asbestos is an effective gene and chromosomal mutagen when assayed using the highly sensitive AL mutation assay and that the mutagenicity is mediated by reactive oxygen species. The objective of the present study is to determine the origin of these radical species, particularly reactive nitrogen species, in fiber mutagenesis. Using the radical probe 5',6'-chloromethyl-2',7'-dihydroxyphenoxazine diacetate to trap reactive radical species, we showed that crocidolite increased the levels of oxyradicals in cytoplasts, in the absence of the nucleus, in a dose-dependent manner, which was reduced significantly by cotreatment with the radical scavenger dimethyl sulfoxide. Treatment of enucleated cells with crocidolite asbestos followed by rescue fusion using karyoplasts from control cells resulted in significant mutant induction, indicating that the nuclear-cytoplasmic interaction is necessary for fiber mutagenesis. Using the fluorescent probe 2,3-diaminonaphthotriazole, crocidolite fibers were shown to induce a dose-dependent increase of nitric oxide production, which was suppressed significantly by concurrent treatment with the nitric oxide synthase inhibitor, NG-methyl-L-arginine (L-NMMA). Similarly, there was a dose-dependent decrease in the mutation yield induced by crocidolites in the presence of graded doses of L-NMMA. These data showed that extranuclear targets play an essential role in the initiation of oxidative damage that mediates fiber mutagenesis in mammalian cells.

• Iron-loaded synthetic chrysotile: a new model solid for studying the role of iron in asbestos toxicity. E. Gazzano, F. Turci, E. Foresti, et al. 2007;20(3):380-7. PubMed · Publisher

  Abstract

  The generation of reactive oxygen species and other radicals, catalyzed by iron ions at the fiber surface, is thought to play an important role in asbestos-induced cytotoxicity and genotoxicity, but a direct confirmation of this statement needs the availability of asbestos samples differing only for their iron content, without the interference of other physicochemical features. Synthetic stoichiometric chrysotile nanofibers, devoid of iron or any other contaminant, did not exert genotoxic and cytotoxic effects nor elicited oxidative stress in a murine alveolar macrophage cell line; on the contrary, the same nanofibers, loaded with 0.57% and 0.94% (w/w) iron, induced DNA strand breaks, lipoperoxidation, inhibition of redox metabolism and alterations of cell integrity, similarly to natural chrysotile. On the other hand, the incubation with ferric nitrilotriacetate, a cell-permeating iron complex, even if it caused an intracellular overloading of iron very similar to that elicited by iron-loaded synthetic chrysotile and by natural chrysotile, did not exert any of these effects. This suggests that chrysotile is not toxic by acting simply as a carrier of iron into the cell, but rather that the redox activity of iron is potentiated when organized at the fibers surface into specific crystallographic sites having coordination states able to activate free radical generation. Synthetic chrysotile fibers may be proposed as a standard reference sample and model solids for experimental studies on asbestos fibers aiming to clarify the mechanisms of its toxicity and to synthesize new fibers devoid of pathogenic effects.

• Ascorbic acid modifies the surface of asbestos: possible implications in the molecular mechanisms of toxicity. G. Martra, M. Tomatis, I. Fenoglio, et al. 2003;16(3):328-35. PubMed · Publisher

  Abstract

  Ascorbic acid is one of the major components of the antioxidants defenses of the lung lining layer where inhaled asbestos fibers are deposited. Crocidolite fibers were incubated at 37 degrees C in a 0.01 M aqueous solution of ascorbic acid for 25 days in order to investigate modifications in surface reactivity. Iron (820 nmol/mg) and monomeric silica (470 nmol/mg) were released in the supernatant, while ascorbic acid was consumed. The amount of iron and silicon released, respectively, 17 and 6% (in atoms) of the total fiber content, exceeded what was expected at the surface, suggesting a partial disgregation of crocidolite promoted by ascorbic acid. In the absence of ascorbic acid but at the same pH, the release of iron and monomeric silica was minimal. At time intervals, aliquots of fibers were withdrawn to evidence chemical modifications progressively taking place. Three families of Fe(II) centers, differing in coordinative unsaturation and progressively removed during incubation, have been evidenced from the FTIR spectra of NO adsorbed onto the fibers. The most uncoordinated ones are removed first. New highly uncoordinated iron sites are exposed at the fiber surface as a consequence of the erosion of the outmost layers while hydration of silica tetrahedra yields new silanol groups. The activity in the Fenton-like reaction (*OH from H(2)O(2)) decreases following surface iron depauperation. Conversely, the homolytic cleavage of the C-H bond (CO(2)*-) from the formate ion) appears related to the small fraction of iron ions always present but easily quenched by the adsorption of ascorbic acid or its oxidation products.

• An ESR and HPLC-EC assay for the detection of alkyl radicals. C.P. Novakov, D. Feierman, A.I. Cederbaum, et al. 2001;14(9):1239-46. PubMed · Publisher

  Abstract

  The correlation of lipid peroxidation with release of alkanes (RH) is considered a noninvasive method for the in vivo evaluation of oxidative stress. The formation of RH is believed to reflect a lipid hydroperoxide (LOOH)-dependent generation of alkoxyl radicals (LO*) that undergo beta-scission with release of alkyl radicals (R*). Alternatively, R* could be spin-trapped with a nitrone before the formation of RH and analyzed by ESR. Extracts from the liver and lung of CCl(4)- and asbestos-treated rats that were previously loaded with nitrones exhibited ESR spectra suggesting the formation of iso-propyl, n-butyl, ethyl, and pentyl radical-derived nitroxides. In biological systems, various nitroxides with indistinguishable ESR spectra could be formed. Hence, experiments with N-tert-butyl-alpha-phenylnitrone (PBN) for spin trapping of R* were carried out in which the nitroxides formed were separated and analyzed by HPLC with electrochemical detection (EC). The C(1-5) homologous series of PBN nitroxides and hydroxylamines were synthesized, characterized by ESR, GC-MS, and HPLC-EC, and used as HPLC standards. For in vivo generation and spin trapping of R*, rats were loaded with CCl(4) and PBN. The HPLC-EC chromatograms of liver extracts from CCl(4)-treated rats demonstrated the formation of both the nitroxide and hydroxylamine forms of PBN/*CCl(3), as well as the formation of a series of unidentified PBN nitroxides and hydroxylamines. However, formation of PBN adducts with retention times similar to these of the PBN/C(2-5) derivatives was not observed. In conclusion, we could not correlate the production of PBN-detectable alkyl radicals with the reported CCl(4)-dependent production of C(1-5) alkanes. We speculate that the major reason for this is the low steady-state concentrations of R* produced because only a small fraction of LO* undergo beta-scission to release R*.

• Using in vitro iron deposition on asbestos to model asbestos bodies formed in human lung. Z. Shen, D. Bosbach, M.F. Hochella, et al. 2000;13(9):913-21. PubMed · Publisher

  Abstract

  Recent studies have shown that iron is an important factor in the chemical activity of asbestos and may play a key role in its biological effects. The most carcinogenic forms of asbestos, crocidolite and amosite, contain up to 27% iron by weight as part of their crystal structure. These minerals can acquire more iron after being inhaled, thereby forming asbestos bodies. Reported here is a method for depositing iron on asbestos fibers in vitro which produced iron deposits of the same form as observed on asbestos bodies removed from human lungs. Crocidolite and amosite were incubated in either FeCl(2) or FeCl(3) solutions for 2 h. To assess the effect of longer-term binding, crocidolite was incubated in FeCl(2) or FeCl(3) and amosite in FeCl(3) for 14 days. The amount of iron bound by the fibers was determined by measuring the amount remaining in the incubation solution using an iron assay with the chelator ferrozine. After iron loading had been carried out, the fibers were also examined for the presence of an increased amount of surface iron using X-ray photoelectron spectroscopy (XPS). XPS analysis showed an increased amount of surface iron on both Fe(II)- and Fe(III)-loaded crocidolite and only on Fe(III)-loaded amosite. In addition, atomic force microscopy revealed that the topography of amosite, incubated in 1 mM FeCl(3) solutions for 2 h, was very rough compared with that of the untreated fibers, further evidence of Fe(III) accumulation on the fiber surfaces. Analysis of long-term Fe(III)-loaded crocidolite and amosite using X-ray diffraction (XRD) suggested that ferrihydrite, a poorly crystallized hydrous ferric iron oxide, had formed. XRD also showed that ferrihydrite was present in amosite-core asbestos bodies taken from human lung. Auger electron spectroscopy (AES) confirmed that Fe and O were the only constituent elements present on the surface of the asbestos bodies, although H cannot be detected by AES and is presumably also present. Taken together for all samples, the data reported here suggest that Fe(II) binding may result from ion exchange, possibly with Na, on the fiber surfaces, whereas Fe(III) binding forms ferrihydrite on the fibers under the conditions used in this study. Therefore, fibers carefully loaded with Fe(III) in vitro may be a particularly appropriate and useful model for the study of chemical characteristics associated with asbestos bodies and their potential for interactions in a biosystem.

1990s

• Mobilization of iron from urban particulates leads to generation of reactive oxygen species in vitro and induction of ferritin synthesis in human lung epithelial cells. K.R. Smith, A.E. Aust. 1997;10(7):828-34. PubMed · Publisher

  Abstract

  Many of the biochemical effects of asbestos in cultured cells have been shown to be due to iron, which can be as high as 27% by weight. Urban air particulates also contain iron, and some of the pathological effects after inhalation may be due to reactive oxygen species produced by iron-catalyzed reactions. Two standard reference material (SRM) urban air particulate samples were used for the studies described here. SRM 1648 (3.9% iron by weight) was collected in the St. Louis, MO, area, and SRM 1649 (3% iron by weight) was collected in the Washington, DC, area. To determine if iron associated with urban particulates could be mobilized, as it is from asbestos, SRMs 1648 and 1649 were incubated with 1 mM citrate or EDTA, in the presence or absence of ascorbate. Iron was mobilized from both particulates by either chelator, especially in the presence of ascorbate. Citrate, in the presence of ascorbate, mobilized 30.9 nmol of Fe/mg of SRM 1648 and 65.1 nmol of Fe/mg of SRM 1649 in 24 h. EDTA, in the presence of ascorbate, mobilized 53.8 nmol of Fe/mg of SRM 1648 and 98.8 nmol of Fe/mg of SRM 1649 in 24 h. To determine whether reactive oxygen species were being produced by the particulate iron, each particulate was incubated with phi X174 RFI DNA in the presence or absence of ascorbate. Single-strand breaks (SSBs) were produced by either particulate, but only in the presence of ascorbate. Incubation of SRM 1648 or 1649 (0.5 mg/mL) with DNA in the presence of ascorbate and citrate resulted in 20% or 34% DNA with SSBs, respectively. Incubation of SRM 1648 or 1649 (0.1 mg/mL) with DNA in the presence of ascorbate and EDTA resulted in 26% or 45% DNA with SSBs, respectively. To determine if iron associated with urban particulates could be mobilized by human lung epithelial cells (A549), cells were treated with particulates and the amount of the iron storage protein ferritin was determined at the end of treatment. The 6.4- or 8.4-fold increase in ferritin observed in cells treated with SRM 1648 or 1649, respectively, over that of control (untreated) cells strongly suggested that iron was mobilized in the cultured cells. If similar mobilization and reactivity of the iron occurs in the lung, this may explain some of the pathological effects of urban particulates.

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