Archives of Biochemistry and Biophysics

Our medical research library holds 19 studies published in Archives of Biochemistry and Biophysics (1984–2023). 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. 19 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Elsevier
• Published: 1951 to the present, United States
• Language: English
• ISSN: 0003-9861 (print), 1096-0384 (electronic)
• Continues: Archives of Biochemistry
• Absorbed: Molecular Cell Biology Research Communications
• Its record in the NLM Catalog

2020s

• Iron links endogenous and exogenous nanoparticles. S. Toyokuni, Y. Kong, M. Katabuchi, et al. 2023;745:109718. PubMed · Publisher

  Abstract

  Current progress in biology and medical science is based on the observation at the level of nanometers via electron microscopy and computation. Of note, the size of most cells in higher species exists in a limited range from 5 to 50 μm. Recently, it was demonstrated that endogenous extracellular nanoparticles play a role in communication among various cellular types in a variety of contexts. Among them, exosomes in serum have been established as biomarkers for human diseases by analyzing the cargo molecules. No life on the earth can survive without iron. However, excess iron can be a risk for carcinogenesis in rodents and humans. Nano-sized molecules may cause unexpected bioeffects, including carcinogenesis, which is a process to establish cellular iron addiction with ferroptosis-resistance. Asbestos and carbon nanotubes are the typical examples, leading to carcinogenesis by the alteration of iron metabolism. Recently, we found that CD63, one of the representative markers of exosomes, is under the regulation of iron-responsive element/iron-regulatory protein system. This is a safe strategy to share excess iron in the form of holo-ferritin between iron-sufficient and -deficient cells. On the other hand, damaged cells may secrete holo-ferritin-loaded exosomes as in the case of macrophages in ferroptosis after asbestos exposure. These holo-ferritin-loaded exosomes can cause mutagenic DNA damage in the recipient mesothelial cells. Thus, there is an iron link between exogenous and endogenous nanoparticles, which requires further investigation for better understanding and the future applications.

  Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

2010s

• Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials. H. Nagai, S. Toyokuni. 2010;502(1):1-7. Review PubMed · Publisher

  Abstract

  Nano-sized durable fibrous materials such as carbon nanotubes have raised safety concerns similar to those raised by asbestos. However, the mechanism by which particulates with ultrafine structure cause inflammation and ultimately cancer (e.g. malignant mesothelioma and lung cancer) is largely unknown. This is partially because the particulates are not uniform and they vary in a plethora of factors. Such variances include length, diameter, surface area, density, shape, contaminant metals (including iron) and crystallinity. Each of these factors is involved in particulate toxicity both in vitro and in vivo. Thus, the elicited biological responses are incredibly complicated. Various kinds of fibers were evaluated with different cells, animals and methods. The aim of this review is to concisely summarize previous reports from the standpoint that activation of macrophages and mesothelial injury are the two major mechanisms of inflammation and possibly cancer. Importantly, these two mechanisms appear to be interacting with each other. However, there is a lack of data on the interplay of macrophage and mesothelium especially in vivo. Since fibrous nanomaterials present potential applications in various fields, it is necessary to develop standard evaluation methods to minimize risks for human health.

  Copyright 2010 Elsevier Inc. All rights reserved.

2000s

• Influence of metal ions on flavonoid protection against asbestos-induced cell injury. V.A. Kostyuk, A.I. Potapovich, E.N. Vladykovskaya, et al. 2001;385(1):129-37. PubMed · Publisher

  Abstract

  Influence of metal ions (Fe2+, Fe3+, Cu2+, Zn2+) on the protective effect of rutin, dihydroquercetin, and green tea epicatechins against in vitro asbestos-induced cell injury was studied. Metals have been found to increase the capacity of rutin and dihydroquercetin to protect peritoneal macrophages against chrysotile asbestos-induced injury. The data presented here show that this effect is due to the formation of flavonoid metal complexes, which turned out to be more effective radical scavengers than uncomplexed flavonoids. At the same time epicatechins and their metal complexes have similar antiradical properties and protective capacities against the asbestos induced injury of macrophages. Metal complexes of all flavonoids were found to be considerably more potent than parent flavonoids in protecting red blood cells against asbestos-induced injury. It was also found that the metal complexes of all flavonoids were absorbed by chrysotile asbestos fibers considerably better than uncomplexed compounds and probably for this reason flavonoid metal complexes have better protective properties against asbestos induced hemolysis. Thus, the results of the present study show that flavonoid metal complexes may be effective therapy for the inflammatory response associated with the inhalation of asbestos fiber. The advantage of their application could be the strong increase in ROS scavenging by flavonoids and finally a better cell protection under the conditions of cellular oxidative stress.

1990s

• Antiradical and chelating effects in flavonoid protection against silica-induced cell injury. V.A. Kostyuk, A.I. Potapovich. 1998;355(1):43-8. PubMed · Publisher

  Abstract

  Quercetin, dihydroquercetin, and rutin are capable of scavenging superoxide anion (rate constants of the reaction with superoxide at pH 10 were 1.7 x 10(5), 1.5 x 10(5), and 0.5 x 10(5) M-1 s-1, respectively). At the same time rutin and quercetin but not dihydroquercetin are iron ion chelators. These substances were used to elucidate the role of radical scavenging and iron chelating in flavonoid protection against asbestos-induced oxidative cellular injury. Exposure of rat peritoneal macrophages to chrysotile asbestos fibers resulted in "frustrated" phagocytosis, cell injury, and a LDH release. Quercetin, dihydroquercetin, and rutin were effective in protecting the phagocytic cells against injury caused by asbestos. Moreover, these flavonoids exhibited cellular protection in the same order of effectiveness as that observed for the quenching of superoxide: quercetin > dihydroquercetin > rutin. Exposure of human red blood cells to asbestos fibers also caused progressive cell injury and lysis. Quercetin and rutin protected the red cells (quercetin > rutin), whereas dihydroquercetin was ineffective in preventing asbestos-induced hemolysis. The protective ability of quercetin and rutin may be related to their iron-chelating activity. Due to this these flavonoids can be located on asbestos surface in sites of initiation of free radical reactions and their antiradical moieties can scavenge reactive oxygen species immediately after the appearance. Thus, both antiradical and chelating effects appear to be involved in the flavonoid protection against silica-induced cell injury.

  Copyright 1998 Academic Press.

• Regulation of nitric oxide synthase induction by iron and glutathione in asbestos-treated human lung epithelial cells. S.H. Park, A.E. Aust. 1998;360(1):47-52. PubMed · Publisher

  Abstract

  Treatment of human lung epithelial (A549) cells with crocidolite asbestos resulted in the induction of the inducible form of nitric oxide synthase (iNOS), production of NO, and a dramatic decrease in intracellular reduced glutathione (GSH). Iron, mobilized from the crocidolite fibers (27% iron by weight), and the formation of NO were required for the formation of 2'-deoxy-7-hydro-8-oxoguanosine in the DNA of the A549 cells, but not for the decrease in GSH. Therefore, we investigated the role of GSH and iron in the induction of iNOS in A549 cells by crocidolite. Iron was required for the induction of iNOS by crocidolite. A fivefold higher amount of chrysotile asbestos (3% iron by weight) was required to cause a similar decrease in intracellular GSH and induction of iNOS. In the absence of asbestos, treatment with either buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, or ferric ammonium citrate (FAC), a soluble form of iron, did not result in induction of iNOS. However, iNOS was induced when A549 cells were treated simultaneously with BSO and FAC. The presence of 5 mM N-acetylcysteine prevented induction of iNOS in crocidolite-treated A549 cells. These observations suggest that the induction of iNOS resulted from a decrease in intracellular GSH and the presence of iron from the asbestos fibers.

  Copyright 1998 Academic Press.

• Induction of ferritin synthesis in human lung epithelial cells treated with crocidolite asbestos. R. Fang, A.E. Aust. 1997;340(2):369-75. PubMed · Publisher

  Abstract

  Crocidolite asbestos is a known human carcinogen containing 27% iron by weight. It has previously been shown that iron was mobilized intracellularly from crocidolite after treatment of human lung epithelial cells (A549) and that the toxicity of the fibers was directly related to how much mobilized iron was in the < 10,000 MW (low-molecular-weight, LMW) fraction [C. C. Chao, L.G. Lund, K. R. Zinn, and A. E. Aust (1994) Arch. Biochem. Biophys. 314, 384-391]. The data here show that iron mobilization from crocidolite began immediately after treatment of the A549 cells and increased linearly with time. However, the synthesis of ferritin, an iron storage protein, did not begin until after 4 h of treatment, reaching a sustained maximum after 12 h. Mobilized iron was preferentially incorporated into the nonferritin-protein fraction up to 7 h after treatment, when the amount of iron mobilized was low and before significant accumulation of newly synthesized ferritin had occurred. This suggested that these cultured cells needed additional iron for synthesis of iron-requiring proteins and that iron mobilized from crocidolite could be utilized directly for this purpose. Subsequent to this, additional mobilized iron was incorporated into newly synthesized ferritin. Even though iron from crocidolite was incorporated into newly synthesized ferritin or into other proteins, the amount of iron from crocidolite in the LMW fraction remained constant during the 24 h. Thus, it appeared that synthesis of ferritin may not have fully protected the cells from the toxic effects of iron mobilized from crocidolite.

• Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells. C.C. Chao, S.H. Park, A.E. Aust. 1996;326(1):152-7. PubMed · Publisher

  Abstract

  Treatment of human lung epithelial (A549) cells with crocidolite resulted in the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the DNA, synthesis of mRNA for the inducible form of nitric oxide synthase (NOS), and increased intracellular nitrite (NO2-), a stable oxidation product of NO. Iron, associated with crocidolite, was involved in both NO2- and 8-OHdG formation. Addition of the NOS inhibitor, aminoguanidine (AG), reduced intracellular NO2- and prevented formation of 8-OHdG in crocidolite-treated cells, suggesting that NO was required in 8-OHdG formation. Addition of an NO-generating compound, diethyltriamine/NO, with AG and crocidolite resulted in recovery of 8-OHdG, further supporting a role for NO in oxidation of deoxyguanosine.

• Effect of iron acquisition on induction of DNA single-strand breaks by erionite, a carcinogenic mineral fiber. S.K. Eborn, A.E. Aust. 1995;316(1):507-14. PubMed · Publisher

  Abstract

  It has been proposed that iron from inhaled fibers, such as asbestos, is responsible for their toxicity and carcinogenicity. The natural fibrous zeolite erionite is far more carcinogenic than asbestos, but contains little or no iron. Fibers that persist in the lung accumulate iron on their surfaces. The ability of erionite to induce formation of single-strand breaks in phi X174 RFI DNA was investigated before and after binding of iron. Unmodified erionite did not induce DNA single-strand breaks with or without ascorbate and/or the iron chelator EDTA. When erionite (1 mg/ml) was suspended in 25, 50, 100, or 500 microM FeCl2, it readily bound iron (25, 50, 93, or 176 nmol Fe/mg, respectively, in 1 h), apparently through ion exchange. When erionite was suspended in FeCl3 at identical concentrations for 1 h, it also bound iron (24, 46, 89, or 239 nmol Fe/mg). The ferric iron did not appear to bind primarily through ion exchange, but appeared to be deposited on the surface, probably in the form of hydroxides/oxyhydroxides. When ferrous iron was bound to erionite, single-strand breaks in DNA were induced in the absence of ascorbate, but when ferric iron was bound, DNA single-strand breaks were observed only in the presence of ascorbate. When EDTA or citrate was added, this activity increased with the amount of iron mobilized from the fiber. If iron acquired by erionite in vivo is similarly mobilized, it may damage biomolecules throughout the cell, including DNA. This may explain the toxicity and carcinogenicity of erionite.

• DNA strand breaks following in vitro exposure to asbestos increase with surface-complexed [Fe3+]. A.J. Ghio, T.P. Kennedy, J.G. Stonehuerner, et al. 1994;311(1):13-8. PubMed · Publisher

  Abstract

  Surface functional groups on silicate dusts complex iron cations which can cycle through reduction and oxidation states to generate free radicals. These oxidants have a capacity to produce DNA strand breaks and mutations which are primary events in cancer induction. A differential in the capacity of fibrous silicates to produce carcinoma is recognized with the amphiboles demonstrating a greater biologic effect than the serpentine fiber chrysotile. We tested the hypothesis that the differences in genotoxicity of these fibrous silicates correspond to varying concentrations of iron complexed to the surface. Relative to chrysotile, the amphibole fibers complexed greater amounts of iron cations from both inorganic and in vivo sources. Increased concentrations of surface-complexed iron were associated with greater oxidant generation, measured as thiobarbituric acid-reactive products of deoxyribose, and more covalently closed, circular DNA strand scission. These results indicate that genotoxic effects of these fibers may correspond to their capacity to complex iron at the surface.

• Effect of long-term removal of iron from asbestos by desferrioxamine B on subsequent mobilization by other chelators and induction of DNA single-strand breaks. C.C. Chao, A.E. Aust. 1994;308(1):64-9. PubMed · Publisher

  Abstract

  The long-term removal of iron from crocidolite or amosite by desferrioxamine B (DF) at pH 7.5 or 5.0 was studied. Crocidolite or amosite (1 mg/ml) was suspended in 50 mM NaCl at pH 7.5 or 5.0 with the addition of 1 mM DF for up to 90 days. Although the rate of iron mobilization decreased with time, iron was continuously mobilized from both forms of asbestos at pH 5.0 or 7.5. The amount of iron mobilized from crocidolite was at least twice that mobilized from amosite at either pH. Iron was mobilized more rapidly from crocidolite at pH 5.0 than at 7.5 for the first 15 days, but at later times the amount being mobilized at pH 7.5 became equal to or slightly greater than that at 5.0. For amosite, the mobilization at pH 5.0 was always greater than that at pH 7.5. Next, the effect of iron removal from asbestos by DF on subsequent iron mobilization by a second chelator (EDTA or citrate) and on induction of DNA single-strand breaks (SSBs) was studied. Asbestos, treated for up to 15 days with DF at pH 7.5, was washed to remove ferrioxamine and excess DF, then incubated with EDTA or citrate (1 mM). The rates of iron mobilization from both forms of asbestos by a second chelator decreased as more and more iron was removed by DF. Induction of DNA SSBs also decreased, reflecting the unavailability of iron to catalyze the damage. The results suggest three things. First, if long-term mobilization of iron from asbestos occurs in vivo as has been observed in vitro, it may play a role in the long-term biological effects of asbestos. Second, more rapid mobilization of iron from asbestos fibers may occur when the fibers are phagocytized by cells and maintained in phagosomes where the pH is 4.0-5.0. Third, treatment of asbestos by iron chelators, such as DF, prior to exposure to cultured cells or whole animals, may reduce the biological effects of asbestos resulting from iron, but may not completely eliminate them.

• Iron mobilization from crocidolite asbestos by human lung carcinoma cells. C.C. Chao, L.G. Lund, K.R. Zinn, et al. 1994;314(2):384-91. PubMed · Publisher

  Abstract

  Neutron-activated crocidolite, containing 55Fe and 59Fe, was used to determine whether iron was mobilized from crocidolite phagocytized by cultured human lung carcinoma cells (A549 cells). Cells were treated with neutron-activated crocidolite in medium at pH 6.8 or 7.4 for 24 h. The mobilization of iron into two subcellular fractions, 10,000g supernatant (total iron) or < 10,000 MW [low-molecular-weight (LMW)] was monitored using scintillation counting. Iron was mobilized from crocidolite at a rate similar to that observed in vitro when citrate was incubated with crocidolite for 24 h at pH 7.4, but the amount mobilized was greater when cells were cultured at pH 6.8 than at 7.4. Iron mobilization was not due to the medium nor did it appear to be due to differences in the amount of crocidolite phagocytized. At the highest concentration of crocidolite used for treatment at pH 7.4 (4.5 micrograms/cm2), a total of 3600 pmol iron/10(6) cells was mobilized of which 54 pmol/10(6) cells was in a LMW fraction. After estimation of the volume of the cells, this was calculated to be equivalent to an intracellular concentration of 1.4 mM iron of which 22 microM was in the LMW fraction. Cell survival decreased linearly as the iron mobilized into the LMW fraction increased, independent of the pH of the culture medium being used. These results suggest that iron mobilization from crocidolite into a LMW fraction may represent "iron overload" in cells which have phagocytized the fibers and may be responsible for crocidolite-dependent cytotoxicity and possibly other crocidolite-dependent biological effects.

• Phagocyte-generated superoxide reduces Fe3+ to displace it from the surface of asbestos. A.J. Ghio, J. Stonehuerner, M.P. Steele, et al. 1994;315(2):219-25. PubMed · Publisher

  Abstract

  Injury after exposure to mineral oxide dusts is considered to be mediated by free radical generation. In vitro production of hydroxyl radical by a fibrous silicate increases with the [Fe3+] complexed to the dust surface. The study hypothesis tested was that extracellular fluids and phagocytic cells can decrease concentrations of iron complexed to the surface of a fibrous silicate by employing host chelators and reductants. Such a depletion of surface [Fe3+] would predict decrements in both oxidant generation and the resultant injury after inhalation and instillation of these mineral oxides. Crocidolite (2.0 mg) which was exposed to either 5.0 ml rat plasma or 10.0 ml rat lavage fluid for 1 h had diminished surface [Fe3+]. Similarly, incubations of crocidolite (2.0 mg) with either 10.0 ml rat alveolar macrophages (1.0 x 10(6) cells/ml) or 10.0 ml rat neutrophils (1.0 x 10(7) cells/ml) decreased concentrations of surface iron. In vivo exposures of asbestos contained in chambers allowing or precluding inflammatory cell entry revealed that the influx of phagocytes was associated with greater decreases in surface [Fe3+]. The body chelators transferrin and lactoferrin were unable to extract the metal from fiber surface in vitro. However, superoxide generated by phagocytes did displace the iron from the crocidolite surface. We conclude that extracellular fluids and phagocytic cells have a capacity to diminish [Fe3+] complexed to the surface of asbestos and therefore decrease the potential for oxidative stress and injury to a living system after exposure to these dusts.(ABSTRACT TRUNCATED AT 250 WORDS)

• Generation of hydroxyl radical by crocidolite asbestos is proportional to surface [Fe3+]. A.J. Ghio, J. Zhang, C.A. Piantadosi. 1992;298(2):646-50. PubMed · Publisher

  Abstract

  Differences among fibrous silicates to effect injury in biological systems have been postulated to reflect oxidant generation by structural iron within the crystal lattice of amphiboles. Iron is also coordinated to the surface of all silicates in concentrations which depend on the density of acidic functional groups. We tested the hypothesis that oxidant generation by crocidolite is proportional to surface-complexed iron rather than variance in the lattice concentrations of this transition metal. Surface iron was quantified after its reduction to Fe2+ and chelation by citrate. Thiobarbituric acid (TBA) reactive products and dihydroxybenzoic acid products of salicylate were employed as indices of nonspecific oxidant and hydroxyl radical generation, respectively. Surface iron, TBA reactive products, and dihydroxybenzoic acid products all diminished after pretreatment of crocidolite with the metal chelator deferoxamine in concentrations varying from 0 to 250 mM. Inclusion of deferoxamine in the reaction mixture provided similar results of diminishing both TBA reactive products and dihydroxybenzoic acid generation. We conclude that oxidant generation by crocidolite is proportional to surface concentrations of iron which can be chelated using deferoxamine. The design of synthetic fibers without health effects after exposure will likely necessitate decreasing the number of surface acidic functional groups to diminish the capacity to complex iron (i.e., minimize the percentage SiO2).

• Mobilization of iron from crocidolite asbestos by certain chelators results in enhanced crocidolite-dependent oxygen consumption. L.G. Lund, A.E. Aust. 1991;287(1):91-6. PubMed · Publisher

  Abstract

  The reactivity of iron on crocidolite asbestos with dioxygen was determined and compared with iron mobilized from crocidolite. Ferrozine, a strong Fe(II) chelator, was used to demonstrate that iron on crocidolite was redox active. More Fe(II) was mobilized from crocidolite (1 mg/ml) by ferrozine anaerobically (11.2 nmol/mg crocidolite/h) than aerobically (6.6 nmol/mg/h) in 50 mM NaCl, pH 7.5, suggesting that Fe(II) on crocidolite reacts with O2 upon aqueous suspension. However, suspension of crocidolite in 50 mM NaCl, pH 7.5, did not result in a measurable amount of O2 consumption. The addition of reducing agents (1 mM) increased the amount of Fe(II) on crocidolite, and addition of ascorbate resulted in 0.4 nmol O2 consumed/mg crocidolite/min. Therefore, iron on crocidolite had limited redox activity in the presence of ascorbate. However, mobilization of iron from crocidolite increased its redox activity. Citrate, nitrilotriacetate (NTA), or EDTA (1 mM) mobilized 79, 32, or 58 microM iron, respectively, in preincubations up to 76 h, and increased O2 consumption upon addition of ascorbate to 2.8, 7.6, or 22.0 nmol O2 consumed/mg/min, respectively. This activity depended only upon the presence of a component(s) mobilized from crocidolite by the chelators. Pretreatment of crocidolite with the iron chelator desferrioxamine B (10 mM) inhibited O2 consumption. The results of the present study suggest that iron on or in crocidolite is responsible for the redox activity of crocidolite, but that mobilization of iron by chelators such as citrate, NTA, or EDTA greatly enhances its redox activity. Thus, iron mobilization from crocidolite in vivo by low-molecular-weight chelators may lead to the increased production of reactive oxygen species which may damage biomolecules, such as DNA.

• Iron mobilization from asbestos by chelators and ascorbic acid. L.G. Lund, A.E. Aust. 1990;278(1):61-4. PubMed · Publisher

  Abstract

  The ability of chelators and ascorbic acid to mobilize iron from crocidolite, amosite, medium- and short-fiber chrysotile, and tremolite was investigated. Ferrozine, a strong Fe(II) chelator, mobilized Fe(II) from crocidolite (6.6 nmol/mg asbestos/h) and amosite (0.4 nmol/mg/h) in 50 mM NaCl, pH 7.5. Inclusion of ascorbate increased these rates to 11.4 and 4.9 nmol/mg/h, respectively. Ferrozine mobilized Fe(II) from medium-fiber chrysotile (0.6 nmol/mg/h) only in the presence of ascorbate. Citrate and ADP mobilized iron (ferrous and/or ferric) from crocidolite at rates of 4.2 and 0.3 nmol/mg/h, respectively, which increased to 4.8 and 1.0 nmol/mg/h in the presence of ascorbate. Since ascorbate alone mobilized iron from crocidolite (0.5 nmol/mg/h), the increase appeared to result from additional chelation by ascorbate. Citrate also mobilized iron from amosite (1.4 nmol/mg/h) and medium-fiber chrysotile (1.6 nmol/mg/h). Mobilization of iron from asbestos appeared to be a function not only of the chelator, but also of the surface area, crystalline structure, and iron content of the asbestos. These results suggest that iron can be mobilized from asbestos in the cell by low-molecular-weight chelators. If this occurs, it may have deleterious effects since this could result in deregulation of normal iron metabolism by proteins within the cell resulting in iron-catalyzed oxidation of biomolecules.

1980s

• Dusts causing pneumoconiosis generate .OH and produce hemolysis by acting as Fenton catalysts. T.P. Kennedy, R. Dodson, N.V. Rao, et al. 1989;269(1):359-64. PubMed · Publisher

  Abstract

  Silicates causing pneumoconiosis function as Fenton catalysts to generate hydroxyl radicals (.OH) when incubated with hydrogen peroxide and a reducing substance. In contrast, silicates which do not cause pneumoconiosis demonstrate no Fenton activity. Catalytic activity is decreased by pretreatment of silicates with the iron chelators deferoxamine or transferrin. Hemolysis from silicates is decreased by interventions which remove superoxide anion or hydrogen peroxide from the medium, or by pretreatment of dusts with iron chelators. Thus, asbestos and nonfibrous silicates may cause pneumoconiosis through a common oxidant mechanism by catalyzing production of toxic .OH radicals in the lung.

• Tobacco-borne siderophoric activity. M.W. Qian, J.W. Eaton. 1989;275(1):280-8. PubMed · Publisher

  Abstract

  The proinflammatory and carcinogenic effects of cigarette smoking are well known. Recent evidence indicts iron as a powerful promoter of inflammatory processes and, perhaps not coincidentally, the lungs and alveolar macrophages of smokers contain abnormally large amounts of iron. Furthermore, ferruginous compounds such as asbestos exert a powerful synergy with smoking in the causation of pulmonary neoplasia. Indeed, elements in tobacco smoke and asbestos synergistically damage DNA through reactions mediated by the (probably iron-dependent) formation of hydroxyl radical. These considerations prompted the hypothesis that tobacco smoke might contain substances capable of "delocalizing' iron. We find that one or more substances in organic extracts of smoke and unburned tobacco will transfer iron from an aqueous to an immiscible organic phase. This organic solvation requires the prior reduction of iron which can be effected by elements in smoke extracts. The translation of iron into organic phase is dependent on time and on the concentration of iron within the aqueous phase. Organic condensates of smoke will leach iron from rich forms of asbestos (amosite and crocidolite). Perhaps most importantly, exposure of intact human cells (erythrocytes) to dried residues of such condensates causes the accumulation of iron. This iron is evidently intracellular because it is inaccessible to powerful extracellular iron chelator such as deferoxamine. This tobacco-borne siderophoric activity may help explain some of the pathologic consequences of tobacco use as pulmonary inflammation and neoplasia.

• Asbestos catalyzes the formation of the 6-oxobenzo[a]pyrene radical from 6-hydroxybenzo[a]pyrene. P. Graceffa, S.A. Weitzman. 1987;257(2):481-4. PubMed · Publisher

  Abstract

  Crocidolite asbestos catalyzes the oxidation of 6-hydroxybenzo[a]pyrene, a metabolite of benzo[a]pyrene, to the 6-oxobenzo[a]pyrene radical as determined by electron spin resonance spectroscopy. This may be a mechanism whereby inhaled asbestos enhances the incidence of lung cancer induced by cigarette smoke, which contains benzo[a]pyrene.

• Asbestos catalyzes hydroxyl and superoxide radical generation from hydrogen peroxide. S.A. Weitzman, P. Graceffa. 1984;228(1):373-6. PubMed · Publisher

  Abstract

  To understand chemical characteristics of the asbestos minerals which might contribute to tissue damage, the catalytic properties of three different varieties were studied. Using spin trapping techniques it was determined that crocidolite, chrysotile, and amosite asbestos were all able to catalyze the generation of toxic hydroxyl radicals from a normal byproduct of tissue metabolism, hydrogen peroxide. The iron chelator desferroxamine inhibits this reaction, indicating a major role for iron in the catalytic process, and suggesting a possible mechanism by which asbestos toxicity might be reduced.

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