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1.
Inhal Toxicol ; 20(2): 157-65, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18236230

ABSTRACT

NASA is planning to build a habitat on the Moon and use the Moon as a stepping stone to Mars. JSC-1, an Arizona volcanic ash that has mineral properties similar to those of lunar soil, is used to produce lunar environments for instrument and equipment testing. NASA is concerned about potential health risks to workers exposed to these fine dusts in test facilities. The potential toxicity of JSC-1 lunar soil simulant and a Martian soil simulant (JSC-Mars-1, a Hawaiian volcanic ash) was evaluated using human alveolar macrophages (HAM) isolated from volunteers; titanium dioxide and quartz were used as reference dusts. This investigation is a prerequisite to studies of actual lunar dust. HAM were treated in vitro with these test dusts for 24 h; assays of cell viability and apoptosis showed that JSC-1 and TiO2 were comparable, and more toxic than saline control but less toxic than quartz. HAM treated with JSC-1 or JSC-Mars 1 showed a dose-dependent increase in cytotoxicity. To elucidate the mechanism by which these dusts induce apoptosis, we investigated the involvement of scavenger receptors (SR). Pretreatment of cells with polyinosinic acid, an SR blocker, significantly inhibited both apoptosis and necrosis. These results suggest HAM cytotoxicity may be initiated by interaction of the dust particles with SR. Besides being cytotoxic, silica is known to induce shifting of HAM phenotypes to an immune active status. The immunomodulatory effect of the dust simulants was investigated. Treatment of HAM with either simulant caused preferential damage to the suppressor macrophage subpopulation, leading to a net increase in the ratio of activator (RFD1+) to suppressor (RFD1+7+) macrophages, an effect similar to that of treatment with silica. It is recommended that appropriate precautions be used to minimize exposure to these fine dusts in large-scale engineering applications.


Subject(s)
Cosmic Dust/adverse effects , Macrophages, Alveolar/drug effects , Mars , Moon , Apoptosis/drug effects , Biomarkers/analysis , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Female , Flow Cytometry , Humans , Immunophenotyping , Macrophages, Alveolar/immunology , Macrophages, Alveolar/pathology , Male , Necrosis/chemically induced , Phenotype , Quartz/adverse effects , Receptors, Scavenger/drug effects , Receptors, Scavenger/metabolism , Titanium/adverse effects
2.
Inhal Toxicol ; 14(9): 917-28, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12396403

ABSTRACT

Volcanic ashes from Arizona and Hawaii, with chemical and mineral properties similar to those of lunar and Martian soils, respectively, are used by the National Aeronautics and Space Administration (NASA) to simulate lunar and Martian environments for instrument tests. NASA needs toxicity data on these volcanic soils to assess health risks from potential exposures of workers in facilities where these soil simulants are used. In this study we investigated the acute effects of lunar soil simulant (LSS) and Martian soil simulant (MSS), as a complement to a histopathological study assessing their subchronic effects (Lam et al., 2002). Fine dust of LSS, MSS, TiO(2), or quartz suspended in saline was intratracheally instilled into C57Bl/6J mice (4/group) in single doses of 0.1 mg/mouse or 1 mg/mouse. The mice were euthanized 4 or 24 h after the dust treatment, and bronchoalveolar lavage fluid (BALF) was obtained. Statistically significant lower cell viability and higher total protein concentration in the BALF were seen only in mice treated with the high dose of quartz for 4 h and with the high dose of MSS or quartz for 24 h, compared to mice treated only with saline. A significant increase in the percentage of neutrophils was not observed with any dust-treated group at 4 h after the instillation, but was observed after 24 h in all the dust-treated groups. This observation indicates that these dusts were not acutely toxic and the effects were gradual; it took some time for neutrophils to be recruited into and accumulate significantly in the lung. A statistically significant increase in apoptosis of lavaged macrophages from mice 4 h after treatment was found only in the high-dose silica group. The overall results of this study on the acute effects of these dusts in the lung indicate that LSS is slightly more toxic than TiO(2), and that MSS is comparable to quartz. These results were consistent with the subchronic histopathological findings in that the order of severity of lung toxicity was TiO(2) < LSS < MSS < quartz.


Subject(s)
Cosmic Dust/adverse effects , Lung Diseases/chemically induced , Lung/drug effects , Acute Disease , Administration, Inhalation , Animals , Apoptosis , Biomarkers/analysis , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Synergism , Intubation, Intratracheal , Leukocyte Count , Lung/chemistry , Lung/pathology , Lung Diseases/pathology , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/pathology , Male , Mice , Mice, Inbred C57BL , Neutrophils/drug effects , Neutrophils/pathology , Ozone/administration & dosage , Ozone/adverse effects , Proteins/analysis , Silicon Dioxide/adverse effects , Time Factors , Titanium/adverse effects
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