Comparison of inducible nitric oxide synthase gene expression and lung inflammation following intratracheal instillation of silica, coal, carbonyl iron, or titanium dioxide in rats

Journal Article · Fri Jun 27 04:00:00 EDT 1997 · Journal of Toxicology and Environmental Health

DOI:https://doi.org/10.1080/009841097160023· OSTI ID:501799

Blackford, Jr, J A; Dey, R D ^[1]; Jones, W; Castranova, V ^[2]

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1. West Virginia Univ., Morgantown, WV (United States)
2. National Institute for Occupational Health and Safety, Morgantown, WV (United States)

The pulmonary toxicity of the respirable dusts silica, coal, carbonyl iron, and titanium dioxide on alveolar macrophage (AM) and neutrophil (PMN) inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production was investigated. Rats were intratracheally instilled with 5 mg/100 g body weight of silica, coal, carbonyl iron, or titanium dioxide. The dust particles averaged less than 5 {mu}m in diameter. Bronchoalveolar ravage was performed 24 h later. Bronchoalveolar lavage cell (BALC) differentials, iNOS gene expression and NO production by BALC (measured indirectly as NO-dependent chemiluminescence), and lavageable lung protein levels were measured. Analyzed on an equal mass basis, silica, coal, and titanium dioxide dusts increased the production of iNOS-dependent NO by AM. Silica and titanium dioxide both increased the levels of iNOS mRNA while carbonyl iron and coal did not. Each dust caused an increase in PMN, indicating an inflammatory response. Carbonyl iron and titanium dioxide decreased the numbers of AM. Levels of acellular lavageable lung protein were increased by silica, carbonyl iron, and titanium dioxide. When exposure was normalized for an equal number of particles, the pneumotoxic dusts, silica and coal, caused more inflammation and NO production than the nuisance dusts, carbonyl iron and titanium dioxide. Therefore, it appears that particle number is a more appropriate metric of exposure than mass when comparing the relative pathogenicity of dusts of different sizes. Furthermore, since the potency of these dusts (on a particle number basis) to increase iNOS gene expression reflects their inflammatory and pathogenic potential, it is proposed that NO may contribute to the early inflammatory damage observed in the lung following dust exposure. 40 refs., 7 figs., 1 tab.

• OSTI ID: 501799
• Journal Information: Journal of Toxicology and Environmental Health, Journal Name: Journal of Toxicology and Environmental Health Journal Issue: 3 Vol. 51; ISSN 0098-4108; ISSN JTEHD6
• Country of Publication: United States
• Language: English

Related Subjects

56 BIOLOGY AND MEDICINE
APPLIED STUDIES
BIOLOGICAL EFFECTS
COAL
DUSTS
INFLAMMATION
LUNGS
NITRIC OXIDE
RESPONSE MODIFYING FACTORS
SILICA
TITANIUM
TOXICITY