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PubMed1991

Effect of blood leucocyte depletion on the inflammatory response of the lung to quartz.

This study determined the effect of blood leucocyte depletion on the early inflammatory response of the lung to alpha-quartz. F344/N rats were instilled intratracheally with either physiological saline or 2 or 5 mg of alpha-quartz suspended in saline. One day prior to the instillation, half of the rats received an ip injection of rabbit antiserum that had been raised against rat neutrophils. The other half of the rats received an ip injection of normal rabbit serum. One day after the instillation of saline or quartz, the animals were euthanized and observed for changes in blood cell numbers, lung histopathology, and bronchoalveolar lavage fluid (BALF) content of indicators of an inflammatory response and cytotoxicity. The rabbit antiserum depleted the blood of most white blood cells of all types. BALF fluid from saline-instilled animals did not differ between the white blood cell-depleted and the nondepleted animals except for a 20% reduction in numbers of alveolar macrophages in the depleted animals. BALF fluid from the nondepleted, quartz-instilled animals had a dose-dependent increase in content of neutrophils and protein (indicator of an increase in the permeability of the alveolar/capillary barrier) as well as an increase in lactate dehydrogenase and glutathione reductase (cytoplasmic enzymes whose presence extracellularly indicates cytotoxicity), alkaline phosphatase (indicator of type II cell secretory activity), beta-glucuronidase, and acid proteinase (lysosomal enzymes) activities. The higher dose of quartz also elicited an increase in LTB4 and PGE2 content of BALF. GSH content of BALF was decreased by the quartz exposure. The depletion of blood white blood cells prevented the influx of neutrophils into the alveoli of the quartz-exposed rats and decreased the BALF markers of capillary permeability and cytotoxicity (protein content and extracellular cytoplasmic enzymes). The absence of neutrophils in the alveoli had no effect on the lysosomal content of BALF, indicating that the neutrophils were not the source of these enzymes in nondepleted rats exposed to alpha-quartz. The quartz-induced elevation of LTB4 in BALF was not observed in depleted rats, suggesting that neutrophils may be the source of the increase in this leukotriene in the BALF. Both the GSH content and the alkaline phosphatase activity in BALF were enhanced in the absence of alveolar neutrophils. The enhancement of GSH in BALF is consistent with the neutrophils being the source of reactive oxygen species that deplete GSH. The increased alkaline phosphatase activity in the BALF of both the depleted and nondepleted animals is consistent with the type II cell hypertrophy that was induced by quartz instillation and was neutrophil independent.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Phospholipid surfactant adsorption by respirable quartz and in vitro expression of cytotoxicity and DNA damage.

Respirable-sized quartz was treated with a saline dispersion of dipalmitoyl phosphatidylcholine (DPPC), a primary component of pulmonary surfactant, to model the adsorption of phospholipid surfactant onto quartz dust following particle deposition in the bronchoalveolar region of the lung. Control and surfactant-treated dusts were used to challenge lavaged rat pulmonary macrophages in vitro over a 1-week period, to determine the effects of adsorbed surfactant on the expression of quartz cytotoxicity and genotoxicity. DNA damage was determined by the single cell gel electrophoresis 'comet' assay. Untreated quartz induced DNA damage, increasing with dose and with time of incubation of dust with macrophages over a 5 day period. DPPC treatment of quartz suppressed DNA damage through 1 day of macrophage challenge. DNA damage then increased over a 5 day period, to approximately half the positive control (untreated quartz) values. Cytotoxicity was measured by trypan blue dye exclusion and by the Live-Dead fluorescence assay for cell viability. Cytotoxicity of surfactant-treated quartz measured one day after challenge of lavaged macrophages was suppressed to values near those of the negative controls, and then increased over a 1 week incubation period to levels near those expressed by native quartz positive controls. Quartz similarly treated with dioleoyl phosphatidylcholine mixed with DPPC substituted in one acyl group with a boron-containing fluorescent chromophore was used with confocal microscopy to measure particle-associated fluorescent surfactant in cells. Approximately half of the fluorescence intensity was lost over a 1 week period following challenge of lavaged macrophage. Results are discussed in terms of a model of restoration of quartz particle surface toxicity as prophylactic surfactant is removed from particle surface by cellular enzymatic digestion processes.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Oxidant-induced DNA damage by quartz in alveolar epithelial cells.

Respirable quartz has recently been classified as a human carcinogen. Although, studies with quartz using naked DNA as a target suggest that formation of oxyradicals by particles may play a role in the DNA-damaging properties of quartz, it is not known whether this pathway is important for DNA damage in the target cells for quartz carcinogenesis, i.e. alveolar epithelial cells. Therefore, we determined in vitro DNA damage by DQ12 quartz particles in rat and human and alveolar epithelial cells (RLE, A549) using the single cell gel electrophoresis/comet assay. The radical generation capacity of quartz was analysed by electron spin resonance (ESR) and by immunocytochemical analysis of the hydroxyl radical-specific DNA lesion 8-hydroxydeoxyguanosine (8-OHdG) in the epithelial cells. Quartz particles as well as the positive control hydrogen peroxide, caused a dose-dependent increase in DNA strand breaks in both cell lines. DNA damage by quartz was significantly reduced in the presence of the hydroxyl-radical scavengers mannitol or DMSO. The involvement of hydroxyl radicals was further established by ESR measurements and was also demonstrated by the ability of the quartz to induce formation of 8-OHdG. In conclusion, our data show that quartz elicits DNA damage in rat and human alveolar epithelial cells and indicate that these effects are driven by hydroxyl radical-generating properties of the particles.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Airborne respirable silica near a sand and gravel facility in central California: XRD and elemental analysis to distinguish source and background quartz.

Despite the potential toxicity of respirable quartz to humans, little is known about the transport of airborne quartz from sources to receptors and how to distinguish anthropogenically generated quartz from natural background in a receptor sample. Airborne quartz emissions near a sand and gravel facility were determined using PM10 and PM2.5 filter samples collected at four downwind sites (D1: 22 m, D2: 62 m, D3: 259 m, and D4: 745 m from the facility) as well as one upwind site (U1: 1495 m) during summer sampling. X-ray diffraction was used to determine quartz concentration and elemental composition was analyzed using PIXE, XRF, PESA, and HIPS techniques. Elemental composition of the PM samples was used to determine the X-ray mass absorption coefficients that are essential for accurate quartz quantification by XRD. Elemental composition was found to be a useful tool to distinguish source and background crystalline silica. Both PM10 and PM2.5 samples collected at the D1, D2, and D3 sites contained more Si, Al, and Fe and less H, Na, and S, compared to those at the U1 site, whereas site D4 sample compositions were similar to those at the U1 site. A composite variable, SOIL/(H+Na+S), where SOIL = 2.20Al + 2.49Si + 1.63Ca + 1.94Ti + 2.42Fe, was used to distinguish source materials from background. Average dry season quartz concentrations in replicate PM10 samples were 4.6 +/- 0.9) microg m(-3) at U1, 60.6 (+/- 5.4) microg m(3) at D1, 62.4 (+/- 3.6) at D2, 32.6 (+/- 2.1) microg m(-3) at D3, and 9.41 (+/- 0.9) microg m(-3) at D4. The mass fraction of quartz was the highest at the D1 site and decreased with increasing distance from the facility. The mass of PM2.5 samples was too low to determine quartz concentrations. These results identify the facility as the main source of quartz and other silicate minerals downwind of the plant and that the air quality of the most remote sampling site, located approximately 750 m downwind, was still impacted by the facility's activity.

Air Pollutants↗
PubMed2002

Surface modification of quartz inhibits toxicity, particle uptake, and oxidative DNA damage in human lung epithelial cells.

Quartz (crystalline silica) is not consistently carcinogenic across different industries where similar quartz exposure occurs. In addition, there are reports that surface modification of quartz affects its cytotoxicity, inflammogenicity, and fibrogenicity. Taken together, these data suggest that the carcinogenicity of quartz is also related to particle surface characteristics, and so we determined the genotoxic effects of DQ12 quartz particles versus DQ12 whose surface was modified by treating with either aluminum lactate or polyvinylpyridine-N-oxide (PVNO). The different particle preparations were characterized for hydroxyl-radical generation using electron spin resonance (ESR). DNA damage was determined by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and the alkaline comet-assay using A549 human lung epithelial cells. Cytotoxicity was measured using the LDH- and MTT-assays, and particle uptake by the A549 cells was quantified by light microscopy, using digital light imaging evaluation of 800 nm sections. The ability of quartz to generate hydroxyl-radicals in the presence of hydrogen peroxide was markedly reduced upon surface modification with aluminum lactate or PVNO. DNA strand breakage and 8-OHdG formation, as produced by quartz at nontoxic concentrations, could be completely prevented by both coating materials. Particle uptake into A549 cells appeared to be significantly inhibited by the PVNO-coating, and to a lesser extent by the aluminum-lactate coating. Our data demonstrate that respirable quartz particles induce oxidative DNA damage in human lung epithelial cells and indicates that surface properties of the quartz as well as particle uptake by these target cells are important in the cytotoxic and the genotoxic effects of quartz in vitro.

Cell Survival↗
PubMedDate not supplied

Specific toxicity and crystallinity of alpha-quartz in respirable dust samples.

alpha-Quartz dust of respirable size--on inhalation--deposits in the lung, where it may remain for long duration and be a risk factor in the development of silicosis and (with increasing weight of evidence) lung cancer in humans. The risk assessment for these end points is fundamentally based on those properties of alpha-quartz that allow it to persist over time in the lung. For individual samples of respirable alpha-quartz it is likely that the specific toxicity of the alpha-quartz in the sample is related to this residence time, which, in turn, will be a function of its crystallinity because of the latter's potential influence on alpha-quartz's cytotoxicity and solubility. Current X-ray powder diffraction technology allows for the routine assessment of diffraction line broadening by measuring the full-width-at-half-maximum (FWHM) of a diffraction line. The FWHM for any accessible alpha-quartz diffraction line in a sample can then be used to directly assess Murata and Norman's Crystallinity Index for the alpha-quartz. This method greatly enhances the practicability of determining alpha-quartz crystallinity on individual respirable dust microsamples collected by personal sampling. It is likely that the Crystallinity Index will prove to be a useful measure of the specific toxicity of alpha-quartz and, hence, find incorporation into the risk assessment for alpha-quartz exposure.

Crystallization↗
PubMed2007

Ascorbic acid-pretreated quartz enhances cyclo-oxygenase-2 expression in RAW 264.7 murine macrophages.

Exposure to quartz particles induces a pathological process named silicosis. Alveolar macrophages initiate the disease through their activation, which is the origin of the later dysfunctions. Ascorbic acid is known to selectively dissolve the quartz surface. During the reaction, ascorbic acid progressively disappears and hydroxyl radicals are generated from the quartz surface. These observations may be relevant to mammalian quartz toxicity, as substantial amounts of ascorbic acid are present in the lung epithelium. We studied the inflammatory response of the murine macrophage cell line RAW 264.7 incubated with ascorbic acid-treated quartz, through the expression and activity of the enzyme cyclo-oxygenase-2 (COX-2). COX-2 expression and prostaglandin secretion were enhanced in cells incubated with ascorbic acid-treated quartz. In contrast, no changes were observed in cells incubated with Aerosil OX50, an amorphous form of silica. Quantification of COX-2 mRNA showed a threefold increase in cells incubated with ascorbic acid-treated quartz compared with controls. The transcription factors, NF-kappaB, pCREB and AP-1, were all implicated in the increased inflammatory response. Reactive oxygen species (H(2)O(2) and OH(*)) were involved in COX-2 expression in this experimental model. Parallel experiments performed on rat alveolar macrophages from bronchoalveolar lavage confirmed the enhanced COX-2 expression and activity in the cells incubated with ascorbic acid-treated quartz compared with untreated quartz. In conclusion, the selective interaction with, and modification of, quartz particles by ascorbic acid may be a crucial event determining the inflammatory response of macrophages, which may subsequently develop into acute inflammation, eventually leading to the chronic pulmonary disease silicosis.

Animals↗
PubMed1990

The effect of chemical modification of quartz surfaces on particulate-induced pulmonary inflammation and fibrosis in the mouse.

One of the critical steps in the development of crystal-induced lung diseases is thought to be the interaction of crystal surfaces with cell membranes. The effect of chemical modifications of the surface of alpha-quartz on the development of lung disease has been investigated by treating quartz with various organosilanes. The functional groups attached to the quartz surfaces were (-CN), (-CH3), (-NH2), and -(N(CH3)3+). After intratracheal injection of each modified crystal at a constant surface area into mice, pulmonary inflammation and fibrosis were assessed 6 wk postexposure to the crystals by lung wet weight (lung index) and by the level of hydroxyproline in the lung. The crystals showing the highest degree of biologic activity were native quartz, which has a negative charge, -N(CH3)3+ modified quartz, which has a positive charge, and -CN modified quartz, which has no charge. One of the crystals with chemical groups capable of hydrogen bonding, the -NH2 modified quartz, was as unreactive as the crystal preparation modified with a hydrophobic group, -CH3. If the -CH3 and -NH2 modified quartz are compared as a less reactive group with the more reactive native quartz and -N(CH3)3+ modified quartz, these experiments suggest that electrostatic interactions may be more important in determining effective biologic activities than are hydrogen bonding interactions.

Animals↗
PubMed2000

Historical respirable quartz exposures of industrial sand workers: 1946-1996.

BACKGROUND: Besides a clear relationship to silicosis, crystalline silica-quartz-has been associated with lung cancer, nonmalignant renal disease, and auto-immune disease. To study diseases associated with crystalline silica further, NIOSH conducted a cohort mortality study of workers from 18 silica sand plants, which had quarry, crushing, and bagging operations to produce industrial sand. Twelve of these plants also had grinding mills to produce fine silica powder. The historical crystalline silica exposures of workers at these plants were estimated to facilitate exposure-response analyses in the epidemiologic study. METHODS: NIOSH obtained personal respirable dust measurement records from Mine Safety and Health Administration (MSHA) compliance inspections at all 18 plants and from the archives of seven plants which had collected samples. These samples had been analyzed for quartz content by x-ray diffraction. Although no personal samples were available before 1974, impinger dust measurements were reported for 19 silica sand plants in 1946; these data were converted and used to estimate exposures prior to 1974. Statistical modeling of the samples was used to estimate quartz exposure concentrations for workers in plant-job-year categories from the 1930s when mortality follow-up of the cohort began until 1988 when follow-up stopped. RESULTS: Between 1974 and 1996, there were 4,269 respirable dust samples collected at these 18 plants. The geometric mean quartz concentration was 25.9 microg/m(3) (GSD = 10.9) with a range from less than 1 to 11,700 microg/m(3). Samples below 1 microg/m(3) were given a value of 0.5 microg/m(3). Over one-third of the samples -37%) exceeded the MSHA permissible exposure limit value for quartz (PEL = 10 mg/m(3)/(%quartz + 2)) and half (51%) of the samples exceeded the NIOSH recommended exposure limit (REL=50 microg/m(3)). The samples were collected from workers performing 143 jobs within the 18 plants, but too few samples were collected from many of the jobs to make accurate estimates. Therefore, samples were combined into 10 categories of jobs performing similar tasks or located within the same plant area. CONCLUSIONS: The quartz concentrations varied significantly by plant, job, and year. Quartz concentrations decreased over time, with measurements collected in the 1970s significantly greater than those collected later. The modeled exposure estimates improve upon duration of employment as an estimate of cumulative exposure and reduce exposure misclassification due to variation in quartz levels between plants, jobs, and over time. Am. J. Ind. Med. 38:389-398, 2000. Published 2000 Wiley-Liss, Inc.

Humans↗
PubMed2000

Persistent depletion of I kappa B alpha and interleukin-8 expression in human pulmonary epithelial cells exposed to quartz particles.

Chronic inflammation and fibrosis following quartz inhalation has been associated with persistent up-regulation of several "pro-inflammatory" genes, which are commonly regulated by nuclear factor kappa-B (NF-kappaB). Transcription of the NF-kappaB-inhibitor IkappaBalpha is also under NF-kappaB control, and its de novo synthesis is considered to comprise a negative feedback loop in transient inflammation. To investigate this mechanism in particle inflammation, we have studied IkappaBalpha degradation in A549 cells exposed to DQ12-quartz or TiO(2), in relation to the expression of IL-8. Although both quartz and TiO(2) were found to cause IkappaBalpha degradation, only quartz elicited a mild IkappaBalpha depletion, first appearing at 4 h. TiO(2) was found to cause a higher short-term increase in IkappaBalpha mRNA-expression compared to quartz, whereas the early enhancement of IL-8 expression and release was similar for both particles. Up-regulation of IL-8 expression was found to persist with quartz only. Cotreatment with PDTC and curcumin reduced particle-elicited IL-8 response, whereas cycloheximide caused enhancement of IL-8 mRNA expression in both the quartz- and TiO(2)-treated cells. Our results demonstrate that mineral dusts cause IkappaBalpha degradation, a transient increase in de novo synthesis of IkappaBalpha, and enhanced IL-8 expression in human pulmonary epithelial cells. While IkappaBalpha degradation and early IL-8 expression seem to be general particle phenomena, particle-specific characteristics impact on activation of IkappaBalpha gene transcription, apparently accounting for the different proinflammatory IL-8 responses seen with quartz and TiO(2) in the longer term. These observations may provide an explanation for the transient versus the persistent pulmonary inflammatory status and subsequent differences in pathogenic potency of TiO(2) and quartz.

Blotting, Western↗
PubMed2001

Aluminium lactate treatment of DQ12 quartz inhibits its ability to cause inflammation, chemokine expression, and nuclear factor-kappaB activation.

In 1997, an IARC Working Group classified quartz (crystalline silica) as a Group 1 lung carcinogen, but only in some industries, i.e., the quartz hazard is a variable entity. The reactivity of the quartz surface may underlie its ability to cause inflammation, and treatments that ameliorate this reactivity will reduce the quartz hazard. In this study we treated quartz (Q) with aluminium lactate (AL), a procedure that is reported to decrease the quartz hazard, and explored the effect this had on the highly reactive quartz surface and on proinflammatory events in rat lungs. Aluminium lactate-treated quartz showed a reduced surface reactivity as measured by electron spin resonance and the hemolysis assay. Eighteen hours after instillation of Q into the rat lung, there was massive inflammation as indicated by the number of neutrophils in the bronchoalveolar lavage (BAL). In addition, Q induced an increase in BAL macrophage inflammatory protein-2 (MIP-2) while ALQ had no significant effect compared to control. Epithelial damage, as indicated by BAL protein and gamma glutamyl transpeptidase, also increased with Q but not with ALQ. Furthermore, Q induced an increase in MIP-2 mRNA by BAL cells while ALQ had no effect compared to controls. There was an increase in nuclear binding of the transcription nuclear factor kappaB (NF-kappaB) in the Q-exposed BAL cells and again no effect on nuclear NF-kappaB binding in BAL cells from ALQ-exposed rats. In conclusion, treatment of the quartz surface with aluminium lactate reduced the reactivity of the particles both in terms of hydroxyl radical generation and in terms of the induction of molecular signaling events leading to inflammation.

Aluminum Compounds↗
PubMed2006

Induction of CYP1A1 in rat lung cells following in vivo and in vitro exposure to quartz.

Respirable quartz has been classified as a human lung carcinogen, but the mechanism by which quartz exposure leads to lung cancer has not been clarified. Consistently higher risks of lung cancer are reported in smokers with quartz exposure and we therefore hypothesised that quartz exposure may alter the expression of enzyme systems involved in activation/detoxification of pre-carcinogens in cigarette smoke. More specifically we studied cytochrome P4501A1 (CYP1A1) expression using reverse transcriptase polymerase chain reaction and immunohistochemistry (IHC) upon in vitro and in vivo quartz exposure. In vitro incubation of rat lung epithelial cells with DQ12 quartz for 24 h showed a dose-dependent induction of CYP1A1-mRNA. On the other hand, CYP1A1 message was not increased in lung epithelial cells isolated from rats at 3, 28 or 90 days after intratracheal instillation of 2 mg DQ12. Following IHC for CYP1A1 protein in rat lung sections from later time-points (180 and 360 days), we observed an increase in the number of CYP1A1 positive cells. After in vivo quartz exposure, protein expression of the Aryl hydrocarbon receptor (AhR) was increased and nuclear translocation of AhR was observed at the same time-points. In conclusion, our findings demonstrate an effect of quartz exposure on chronic CYP1A1 expression in vivo, whereas the in vitro models show an immediate upregulation. We suggest that this upregulation of CYP1A1 may act as a co-carcinogenic pathway in quartz exposed workers by activation of pre-carcinogens such as those present in cigarette smoke.

Active Transport, Cell Nucleus↗
PubMed1998

The quartz hazard: a variable entity.

An IARC Working Group recently classified crystalline silica (quartz) into IARC's Group 1, i.e. a carcinogen. This classification is based on evidence of carcinogenicity in experimental animals and in humans. However, the evaluation stated that in making the overall evaluation, the Working Group noted that carcinogenicity to humans was not detected in all industrial circumstances studied and that carcinogenicity may be dependent on inherent characteristics of the crystalline silica or on external factors affecting its biological activity. The present review seeks to put the apparently conflicting findings of cancer incidence in quartz-exposed industries into a unifying thesis, based on mechanistic studies. These mechanistic studies have enabled the events leading from deposition of quartz to silicosis and cancer to be partially elucidated and have demonstrated that the biological effects of quartz can be understood in terms of surface reactivity. We particularly emphasise the ability of quartz to generate free radicals and cause oxidative stress and the fact that this could be modified by a range of substances that affect the quartz surface; some of these modifying substances could originate from other minerals. We therefore propose that the hazard posed by quartz is not a constant entity, but one that may vary dramatically depending on the origin of the silica sample or its contact with other chemicals/minerals within its complex constitution. The mechanistic data described here could assist in the interpretation of epidemiological studies and pose further hypotheses that could be tested in order to help resolve the quartz carcinogenesis anomaly. The data suggest that quartz cannot be death with as a single hazard entity, as is the case with most other chemicals.

Animals↗
PubMed2002

Quantification of respirable, thoracic, and inhalable quartz exposures by FT-IR in personal impactor samples from construction sites.

The classification of quartz as a group I human carcinogen by the International Agency for Research on Cancer (IARC) highlights the need to develop a method to assess quartz exposures in the thoracic and inhalable particle size fractions to supplement the current method for the respirable size fraction. Heavy and highway construction operations can produce high respirable quartz exposures, but inhalable and thoracic exposures have not previously been well characterized. These larger particle size fractions may well contribute to the elevated cancers of the buccal cavity, throat, and GI tract in occupational cohorts of construction workers. A description is provided of the application of FT-IR for quartz analysis of personal cascade impactor air samples collected from highway construction sites. Separate calibration curves were generated for each stage of the four-stage personal impactor by using the impactor to sample quartz dust (Min-U-Sil 5 and Min-U-Sil 30) in an aerosol-generating loop. In addition, three separate calibration curves were generated using filters spiked with bulk Min-U-Sil 5, Min-U-Sil 30, and SRM 1878a (a respirable standard from NIST). The results showed that bulk Min-U-Sil 5 and SRM 1878a calibrations were identical and accurately estimated the respirable quartz fraction. Bulk Min-U-Sil 30 underestimated quartz in stages 1, 2, and 3 by 46 percent, 38 percent, and 18 percent, respectively. Using a respirable standard (bulk Min-U-Sil 5 or SRM 1878a) to quantify the larger particle sizes underestimated quartz in stages 1, 2, and 3 by 73 percent, 72 percent, and 63 percent, respectively. Until a standard reference material for quartz is developed for the larger particle sizes, the method described here, with some modifications, can be used to provide estimates of these biologically relevant particle size fractions. The results of this study also reaffirmed the need to collect narrow ranges of particle size in order to minimize quantification errors, since the FT-IR and XRD instrumental response is particle size-dependent.

Air Pollutants, Occupational↗
PubMed2002

DNA damage in lung epithelial cells isolated from rats exposed to quartz: role of surface reactivity and neutrophilic inflammation.

Respirable quartz has been classified as a human lung carcinogen (IARC, 1997). However, the mechanisms involved in quartz-induced carcinogenesis remain unclear. The aim of the present study was to investigate acute DNA damage in epithelial lung cells from rats exposed to quartz. Since surface reactivity is considered to play a crucial role in the toxicity of quartz, the effect of surface modifying agents polyvinylpyridine-N-oxide (PVNO) and aluminium lactate (AL) was evaluated. Therefore, rats were instilled with quartz (DQ12, 2 mg/rat) or quartz treated with PVNO or AL. After 3 days animals were killed and brochoalveolar lavage (BAL) was performed to evaluate inflammatory cell influx. BAL-fluid levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP) and total protein were used as lung damage markers. Neutrophil activation was assessed by myeloperoxidase (MPO) measurement, and total antioxidant capacity of the BAL-fluid was determined using the TEAC (trolox equivalent antioxidant capacity) assay. Lung epithelial cells were isolated and DNA strand breakage was determined by single cell gel electrophoresis (comet assay). DNA damage was significantly increased in epithelial cells from rats instilled with DQ12, whereas no enhanced DNA strand breakage was observed when quartz was treated with PVNO or AL. Total protein, LDH and TEAC were increased in rats treated with native quartz, and this was inhibited by both coatings. A significant correlation between neutrophil numbers and MPO levels was observed, indicating neutrophil activation. Inhibition of DNA damage by both coatings was paralleled by a reduction of neutrophil influx as well as MPO activity. In this study we provide evidence that modification of the particle surface prevents DNA strand breakage in epithelial lung cells from quartz-exposed rats. Furthermore, the present data show the feasibility of our in vivo model to evaluate the role of inflammation, antioxidant status, and cytotoxicity in particle-induced DNA damage.

Alkaline Phosphatase↗
PubMed1983

Comparative effects of inhaled volcanic ash and quartz in rats.

To investigate the relative toxicities of inhaled volcanic ash and quartz, we exposed matched groups of rats to either respirable volcanic ash (100 mg/m3), quartz (100 mg/m3), or clean air only for 6 h daily for 10 days. Thereafter, we examined animals sequentially for as long as 9 months, and measured changes in lung histopathologic aspects, air-space cells and lipids, and lung density. Neutron activation studies demonstrated that 3.3% of the inhaled daily dose of volcanic ash was detectable in the lung parenchyma. Volcanic ash was less toxic to the lung than quartz. Immediately after exposure, the lungs of animals treated with volcanic ash had ultrastructural evidence of damage to type I pneumocytes and early alveolar edema formation. By contrast, quartz-treated animals had an intense acute injury, with intraalveolar accumulation of lipid, protein, macrophages, and granulocytes. Six months after exposure, animals treated with volcanic ash had moderate interstitial thickening and fibrosis, whereas the quartz-treated animals had severe pulmonary fibrosis. Quartz, but not volcanic ash, caused a marked increase in lavage granulocytes, protein, and phospholipids. Lung density increased in quartz-exposed, but not in volcanic-ash-exposed animals. These data indicate that volcanic ash is less harmful to the lung parenchyma than is quartz. Persons exposed to volcanic ash for short periods are at much less risk of subsequent lung damage than are those who are exposed to similar amounts of quartz in the workplace.

Absorptiometry, Photon↗
PubMed2004

Inflammatory time course after quartz instillation: role of tumor necrosis factor-alpha and particle surface.

Inflammation has been suggested as the key factor in the development of quartz-induced fibrosis and carcinogenesis, and particle surface properties are argued as an important characteristic responsible for these pathologic alterations. To evaluate the effect of surface modification on acute and subchronic inflammation, female Wistar rats were intratracheally instilled with 2 mg native quartz, or quartz coated either with polyvinyl-pyridine-N-oxide or with aluminium lactate. Various markers of lung toxicity, inflammation, and oxidative stress were found to be enhanced at 3, 7, 21, and 90 d after instillation of native quartz. Quartz-treated animals also showed enhanced immunostaining of nuclear factor-kappaB (NF-kappaB) in alveolar macrophages and lung epithelium, as well as reduced IkappaBalpha levels in whole lung homogenate. Both surface modifications were found to inhibit most of the effects as observed with native quartz. NF-kappaB activation was also observed in vitro in rat lung epithelial cells following treatment with lavage fluid from quartz-treated animals, as well as with conditioned medium of quartz-treated macrophages, and these effects appeared to be at least partly tumor necrosis factor-alpha-independent. In conclusion, the persistent subchronic inflammatory lung response after quartz exposure appears to be particle surface-driven and is associated with NF-kappaB activation in both alveolar macrophages and the lung epithelium.

Animals↗
PubMed1996

Alpha-quartz-induced chemokine expression by rat lung epithelial cells: effects of in vivo and in vitro particle exposure.

Chemokines are chemotactic cytokines that can play a key role in leukocyte recruitment to sites of tissue injury or infection. Previous studies have demonstrated that exposure to alpha-quartz as well as other noxious particles increases chemokine gene expression in rat lung, although the cells responsible for chemokine expression and the mechanisms underlying this response have remained unclear. The present studies demonstrate that exposure of rats to alpha-quartz induced expression of mRNA for the chemokine macrophage-inflammatory protein (MIP)-2 in epithelial cells lining the terminal bronchioles and alveolar ducts as well as macrophages and alveolar type II cells in the more distal lung. Treatment of rats with an anti-MIP-2 antiserum before alpha-quartz exposure markedly attenuated neutrophilic infiltration of the lungs demonstrating an important role for MIP-2 in alpha-quartz-induced pulmonary inflammation. In vitro exposure of primary cultures of rat alveolar type II cells or the rat alveolar type II cell line RLE-6TN to tumor necrosis factor-alpha, endotoxin, or alpha-quartz increased mRNA for MIP-2 as well as the structurally and functionally similar chemokine cytokine-induced neutrophil chemoattractant but not the chemokine MIP-1 alpha. The alpha-quartz-induced increase in epithelial MIP-2 mRNA resulted, at least in part, from increased gene transcription and was associated with the release of active MIP-2 protein. Induction of RLE-6TN MIP-2 and cytokine-induced neutrophil chemoattractant mRNA expression was not unique to alpha-quartz, being also increased by crocidolite asbestus fibers but not by titanium dioxide or MMVF-10 glass fibers. These findings indicate that epithelial cells contribute to chemokine expression in rat lung after exposure to alpha-quartz and potentially other noxious particles and suggest that alpha-quartz-activated MIP-2 expression in vivo results, at least in part, from a direct action of the particles on the lung epithelium.

Animals↗