RESUMO
Inhaled crystalline quartz is a carcinogen. Analyses show differences in the distribution of lung cancer types depending on the status of silicosis. Using 2,524 lung tumor cases from the WISMUT autopsy repository database, silicosis was differentiated into cases without silicosis in lung parenchyma and its lymph nodes, with lymph node-only silicosis, or with lung silicosis including lymph node silicosis. The proportions of adenocarcinoma, squamous cell carcinoma, and small-cell lung carcinoma mortality for increasing quartz exposures were estimated in a multinomial logistic regression model. The relative proportions of the lung cancer subtypes in lymph node-only silicosis were more similar to lung silicosis than without any silicosis. The results support the hypothesis that quartz-related carcinogenesis in case of lymph node-only silicosis is more similar to that in lung silicosis than in without silicosis.
Assuntos
Neoplasias Pulmonares/etiologia , Doenças Linfáticas/etiologia , Mineradores , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Quartzo/toxicidade , Silicose/etiologia , Adulto , Idoso , Poeira , Alemanha/epidemiologia , Humanos , Exposição por Inalação , Neoplasias Pulmonares/epidemiologia , Doenças Linfáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Silicose/epidemiologia , UrânioRESUMO
This study investigates the association between lymph node-only and lung silicosis in uranium miners with lung cancer and exposure to quartz dust. Tissue slides of 4,384 German uranium miners with lung cancer were retrieved from an autopsy archive and reviewed by 3 pathologists regarding silicosis in the lungs and lymph nodes. Cumulative exposure to quartz dust was assessed with a quantitative job-exposure matrix. The occurrence of silicosis by site was investigated with regression models for exposure to quartz dust. Miners with lung silicosis had highest cumulative quartz exposure, followed by lymph node-only silicosis and no silicosis. At a cumulative quartz exposure of 40 mg/m(3) × years, the probability of lung silicosis was above 90% and the likelihood of lymph node-only silicosis and no silicosis do not differ anymore. The results support that lymph node silicosis can precede lung silicosis, at least in a proportion of subjects developing silicosis, and that lung silicosis strongly depends on the cumulative quartz dose.
Assuntos
Neoplasias Pulmonares/complicações , Doenças Linfáticas/complicações , Mineração/estatística & dados numéricos , Silicose/complicações , Urânio , Idoso , Poeira , Alemanha/epidemiologia , Humanos , Neoplasias Pulmonares/patologia , Doenças Linfáticas/patologia , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Quartzo/toxicidade , Silicose/patologia , Fatores de TempoRESUMO
TiO(2) is considered to be toxicologically inert, at least under nonoverload conditions. To study if there are differences in lung effects of surface treated or untreated TiO(2) we investigated the inflammatory and genotoxic lung effects of two types of commercially available TiO(2) at low doses relevant to the working environment. Rats were exposed by instillation to a single dose of 0.15, 0.3, 0.6, and 1.2 mg of TiO(2) P25 (untreated, hydrophilic surface) or TiO(2) T805 (silanized, hydrophobic surface) particles, suspended in 0.2 ml of physiological saline supplemented with 0.25% lecithin. As control, animals were instilled with the vehicle medium only or with a single dose of 0.6 mg quartz DQ12. At days 3, 21, and 90 after instillation bronchoalveolar lavage was performed and inflammatory signs such as cells, protein, tumor necrosis factor-alpha, fibronectin, and surfactant phospholipids were determined. Additionally, 8 microm frozen sections of the left lobe of the lung were cut and stored at -80 degrees C. The sections were used for immunohistochemical detection of 8-oxoguanine (8-oxoGua) by a polyclonal antibody in the DNA of individual lung cells. In the quartz-exposed animals a strong progression in the lung inflammatory response was observed. Ninety days after exposure a significant increase in the amount of 8-oxoGua in DNA of lung cells was detected. In contrast, animals exposed to TiO(2) P25 or TiO(2) T805 showed no signs of inflammation. The amount of 8-oxoGua as a marker of DNA damage was at the level of control. The results indicate that both types of TiO(2) are inert at applicated doses.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Guanina/análogos & derivados , Pulmão/efeitos dos fármacos , Mutagênicos/toxicidade , Titânio/toxicidade , Poluentes Ocupacionais do Ar/química , Animais , Lavagem Broncoalveolar , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Divisão Celular/efeitos dos fármacos , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Guanina/análise , Instilação de Medicamentos , Pulmão/citologia , Mutagênicos/química , Tamanho da Partícula , Pneumonia/induzido quimicamente , Surfactantes Pulmonares/análise , Quartzo/toxicidade , Ratos , Ratos Wistar , Propriedades de Superfície , Titânio/químicaRESUMO
Exposure to quartz and high concentrations of other poorly soluble particles can lead to the development of lung tumors in the rat. The mechanisms involved in particle-induced carcinogenesis seem to include inflammation-associated production of reactive oxygen species (ROS) and DNA damage. ROS induce 8-oxoguanine (8-oxoGua) and a panel of other oxidation products in DNA. In proliferating cells such DNA lesions can lead to various types of mutations, which might be critical for cancer-related genes with respect to tumor formation. Quartz is known to mediate the induction of 8-oxoGua in the nuclear DNA of lung cells when applied to the lung of rats. We have investigated the time- and dose-dependent biologic effects of quartz and, as a control, corundum, on cell proliferation and various pulmonary inflammation and toxicity markers in rat bronchoalveolar lavage fluid (BALF); on the induction of 8-oxoGua in the DNA of rat lung cells; and on the cellular levels of p53 wild-type and p53 mutant (mut) protein. Rats were exposed by intratracheal instillation to various amounts of quartz (0.3, 1.5, or 7.5 mg/rat) or corundum (0.3, 1.5, or 7.5 mg/rat) and measured at Days 7, 21, and 90 after exposure. Corundum had no adverse effects except a slight elevation of 8-oxoGua at a dose of 7.5 mg/rat. However, significant changes in the BALF were detected at all quartz doses. 8-oxoGua was significantly increased only at 1.5 and 7.5 mg quartz/rat. The amount of cells with detectable p53 wild-type protein levels was increased at 1.5 and 7.5 mg quartz/rat at 7 and 21 d. Elevated amounts of cells with enhanced p53 mut protein levels were measured at all time points after instillation of 7.5 mg quartz/rat.
Assuntos
Dano ao DNA/imunologia , Guanina/análogos & derivados , Pulmão/imunologia , Pneumonia/genética , Pneumonia/imunologia , Quartzo/toxicidade , Óxido de Alumínio/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Guanina/análise , Imuno-Histoquímica , Antígeno Ki-67/análise , Pulmão/química , Pulmão/citologia , Mutagênicos/toxicidade , Neutrófilos/imunologia , Estresse Oxidativo/imunologia , Pneumonia/induzido quimicamente , Proteínas/análise , Ratos , Ratos Wistar , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genéticaRESUMO
Epidemiologic data show that air pollution particulates cause adverse pulmonary health effects, especially in individuals with preexisting lung disease. We sought to model in vitro preexisting lung inflammation in order to investigate the hypothesis that "primed" lung epithelial cells will exhibit enhanced phlogistic responses [e.g., interleukin-8 (IL-8) production] to particulate air pollution. Exposure of tumor necrosis factor alpha (TNF-alpha) primed or control A549 cells to the air pollution particulates, residual oil fly ash (ROFA), and the known pathogenic dust alpha-quartz, but not inert TiO2, caused increased IL-8 production in primed cells compared to normal cells in a concentration-dependent manner (particle concentration range 0-200 microg/ml). We hypothesized that oxidant mechanisms may be involved in the cellular response to particulates. Addition of the antioxidant N-acetylcysteine (NAC, 1.0 mM) decreased ROFA and alpha-quartz-mediated IL-8 production by approximately 50% in normal and TNF-alpha-primed A549 cells. In addition, exposure of A549 cells to ROFA caused a substantial (and NAC inhibitable) increase in oxidant levels as measured by fluorometry (DCFH oxidation). These data suggest that (1) lung epithelial cells primed by inflammatory mediators can show enhanced cytokine production after exposure to air pollution particulates, and (2) oxidant stress is a key mechanism for this response.
Assuntos
Poluição do Ar/efeitos adversos , Células Epiteliais/imunologia , Interleucina-8/biossíntese , Pulmão/imunologia , Estresse Oxidativo , Pneumonia/imunologia , Acetilcisteína/farmacologia , Adenocarcinoma Bronquioloalveolar , Antioxidantes/farmacologia , Carbono/toxicidade , Cromanos/farmacologia , Cinza de Carvão , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Citometria de Fluxo , Fluoresceínas/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Resíduos Industriais/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares , Tamanho da Partícula , Material Particulado , Petróleo/toxicidade , Piperazinas/farmacologia , Pneumonia/patologia , Quartzo/química , Quartzo/toxicidade , Titânio/química , Titânio/toxicidade , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVE: To understand the role of cytokine released from alveolar macrophage (AM) in lung fibrosis caused by mineral dust. METHODS: Rabbit's AM obtained by lavage was cultured with mineral dust in vitro. Activities of tumor necrosis factor (TNF) and interleukin 6 (IL-6) in its supernatant were determined with isotope labelling method and MTT colorimetry, respectively. Human fetal lung fibroblast WI-138 was cultured with this supernatant. Proliferation of fibroblast and synthesis of collagen were examined by 3H-thymidine (3H-TdR) and 14C-proline (14C-Pro) incorporation and its total hydroxyproline (HOP) level was analyzed by chloramine-T method. RESULTS: Proliferation of lung fibroblast and synthesis of collagen could be enhanced by the supernatant containing AM induced by quartz, asbestos and uranium mineral dust, with 3H-TdR incorporated counts per minute (cpm) of 6,584, 3,848 and 6,893 in the group of 100 micrograms 3H-TdR and 14C-Pro incorporated 27,952, 13,416 and 18,538 in the group of 200 micrograms respectively, which were significantly higher than those in the control group. Total HOP levels in the culture media for lung fibroblast enhanced by AM supernatant were 22.41, 24.00 and 21.39 micrograms/ml, respectively, and was significantly higher than that in the control group (12.91 micrograms/ml). Release of TNF and IL-6 could be stimulated by mineral dust, such as quartz, asbestos and uranium mineral dust, and their activities were significantly higher than those in the control group, with those of 1,396, 1,198 and 852 U/ml in TNF group and 1,336, 1511 and 1,335 U/ml in IL-6 group, respectively. Proliferation of lung fibroblast and synthesis of collagen could be inhibited by antibody against TNF and interferon-r (gamma), and the effect of the latter was weaker than that of the former on inhibition of fibroblast proliferation and the effect on collagen synthesis was just in the opposite direction. CONCLUSION: Lung fibrosis caused by mineral dust correlated with abnormal expression of TNF and IL-6. Antibody against TNF and gamma interferon could antagonize the effect of NTF and IL-6.
Assuntos
Poeira , Interleucina-6/metabolismo , Macrófagos Alveolares/metabolismo , Minerais/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Animais , Amianto/toxicidade , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Interferon gama/metabolismo , Masculino , Quartzo/toxicidade , Coelhos , Urânio/toxicidadeRESUMO
Female wistar rats were inoculated intratracheally with 10 mg/ml suspensions of various dusts, viz: quartz, fly ash, mica and corundum in physiological saline. Biochemical markers of bronchoalveolar lavage fluid (BALF) were analysed 8 days after the instillation of the dusts. Elevated levels of proteins, sialic acid and phospholipid contents and the activity of lactate dehydrogenase correlated well with the degree of the known fibrogenic potential of different dusts in the lungs in the following order, quartz greater than fly ash greater than mica greater than corundum. beta-glucuronidase activity, was however, only elevated in the quartz inoculated group of rats. It is suggested that biochemical constituents of BALF analysed shortly after the exposure to different dusts can be useful to mirror alterations in the tissue response to mineral dusts.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Poeira/efeitos adversos , Pulmão/efeitos dos fármacos , Óxido de Alumínio/toxicidade , Silicatos de Alumínio/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/enzimologia , Carvão Mineral/toxicidade , Feminino , Glucuronidase/análise , L-Lactato Desidrogenase/análise , Ácido N-Acetilneuramínico , Fosfolipídeos/análise , Proteínas/análise , Quartzo/toxicidade , Ratos , Ácidos Siálicos/análiseRESUMO
To determine whether macrophages exposed to mineral dusts are altered, rats were exposed intratracheally to one of several mineral dusts, held 8 days, their lungs washed and the cellular composition of the fluid characterized morphologically and functionally. The number of cells recovered from lung washings of exposed rats increased 2 to 5 times relative to control rats; however, the percentage of such cells that were macrophages, or were capable of phagocytosis, adherence to glass or metabolism of carbohydrates via the hexose monophosphate shunt as indicated by reduction of nitroblue tetrazolium, were reduced. Silica dust produced the greatest effect, corresponding qualitatively to earlier in vivo studies.
Assuntos
Macrófagos/efeitos dos fármacos , Minerais/toxicidade , Fagocitose/efeitos dos fármacos , Alvéolos Pulmonares/citologia , Óxido de Alumínio/toxicidade , Silicatos de Alumínio/toxicidade , Animais , Carbono/toxicidade , Células Cultivadas , Cinza de Carvão , Feminino , Contagem de Leucócitos/efeitos dos fármacos , Macrófagos/fisiologia , Material Particulado , Fagocitose/fisiologia , Quartzo/toxicidade , Ratos , Ratos EndogâmicosRESUMO
Recent epidemiologic studies have suggested that some workers exposed to inorganic dusts develop air-flow obstruction independent of or greater than that produced by cigarette smoke; the morphologic basis of this effect is unknown. To investigate this problem, we administered saline alone, 10 mg iron oxide (an inert dust), or 10 or 30 mg of quartz to rats by intratracheal instillation. Animals were killed after 30 days, and pulmonary function and morphologic changes were examined. The iron oxide group was similar to the saline control group in all functional and morphometric parameters. However, both quartz-exposed groups showed evidence of air-flow obstruction, with more severe abnormalities in the high dose group. These findings correlated with morphometric observations of emphysema and thickened airway walls, with changes again more severe in the high dose group. Early silicotic nodules were also present in the latter animals. We conclude that in addition to the classic lesions of nodular silicosis, quartz can produce morphologic and functional changes of air-flow obstruction; no such changes are seen with iron oxide. These observations may explain the air-flow obstruction seen in workers exposed to mineral dusts.
Assuntos
Obstrução das Vias Respiratórias/induzido quimicamente , Enfisema/induzido quimicamente , Compostos Férricos/toxicidade , Quartzo/toxicidade , Doenças Respiratórias/induzido quimicamente , Dióxido de Silício/toxicidade , Obstrução das Vias Respiratórias/patologia , Obstrução das Vias Respiratórias/fisiopatologia , Animais , Brônquios/patologia , Enfisema/patologia , Enfisema/fisiopatologia , Feminino , Ratos , Ratos Endogâmicos , Testes de Função Respiratória , Doenças Respiratórias/patologia , Doenças Respiratórias/fisiopatologiaAssuntos
Óxido de Alumínio/toxicidade , Silicatos de Alumínio/toxicidade , Alumínio/toxicidade , Macrófagos/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Quartzo/toxicidade , Dióxido de Silício/toxicidade , Titânio/toxicidade , Animais , Poeira , Espectroscopia de Ressonância de Spin Eletrônica , Técnicas In Vitro , Cavidade Peritoneal/citologia , Fibrose Pulmonar/induzido quimicamente , RatosRESUMO
Guinea pig peritoneal macrophages were incubated in vitro with various concentrations of selenium (as sodium selenite), quartz, and quartz + selenite. Cellular viability, adhesiveness, migration, and lipid peroxide content as parameters for cytotoxicity were studied. A dose-dependent cytotoxic response of macrophages to selenite was observed. Selenite concentrations of 10(-6), 10(-5), and 10(-4) M were shown to be nontoxic in the various test procedures. Quartz treatment of macrophages reduced cell viability, adhesiveness, and migration, and enhanced lipid peroxide release. Cotreatment of macrophages with nontoxic selenite concentrations suppressed significantly the cytotoxic effects induced by quartz and was effective in reducing the high rate of lipid peroxidation. The results provide support for the role of selenium in the stabilization of macrophage membrane damaged by quartz.
Assuntos
Macrófagos/efeitos dos fármacos , Quartzo/toxicidade , Selênio/farmacologia , Dióxido de Silício/toxicidade , Adesividade , Animais , Líquido Ascítico , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Interações Medicamentosas , Cobaias , Peróxidos Lipídicos/metabolismo , Fatores Inibidores da Migração de MacrófagosRESUMO
As a first step in the development of an animal model for determining the role of pulmonary fibrosis in the etiology and pathogenesis of lung cancer, the fibrogenic potential of quartz, quartz and ferric oxide administered together, fibrous glass, and hydrated alumina were studied by multiple intratracheal instillation in groups of male Lak:LVG Syrian golden hamsters. Dose-related decreases in survival were evident for the groups instilled with the two highest doses of quartz or quartz and ferric oxide. Instillation of quartz or quartz and ferric oxide induced the greatest pulmonary fibrosis in response to the materials tested. However, the dense fibrous tissue present in the lungs in classical human silicosis and in experimental silicosis of rats was not observed in this study. The results of this study indicate that the Syrian golden hamster is not a suitable species for studying the role of quartz-induced pulmonary fibrosis in pulmonary carcinogenesis.