Can toxicogenomics provide information on the bioreactivity of diesel exhaust particles?

• Published in: Toxicology (Amsterdam) 2001-08, Vol.165 (2), p.145-152
• Main Authors: Reynolds, Lucy J., Richards, Roy J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Conventional toxicology; Diesel exhaust particles; DNA, Complementary - genetics; Gene Expression Profiling - methods; Gene Expression Regulation - drug effects; Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.); Lung - drug effects; Lung - metabolism; Lung - physiology; Macroarrays; Male; Medical sciences; Oligonucleotide Array Sequence Analysis - methods; Particle Size; Particulate matter with an aerodynamic diameter less than 10 microns; Rats; Rats, Sprague-Dawley; Toxicity Tests - methods; Toxicogenomics; Toxicology; Vehicle Emissions - toxicity
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(01)00417-6

Epidemiologists have linked increased cardio-respiratory hospital admissions, morbidity and mortality rates and increases in particulate matter with an aerodynamic diameter less than 10 microns (PM10) concentrations ( Anderson et al., 1991). PM10 consist of a heterogeneous mixture of particles that include minerals, metal oxides, sea salt, biological components and soot. In urban locations, soot, especially ultrafine diesel exhaust particles (DEP), accounts for 20–80% by mass of the airborne PM10 arising from vehicular activities. In the experiment described here, control [NaCl] and 1.25 mg of DEP were instilled into rat lung and the responses assessed using changes in lung permeability, inflammation and epithelial cell markers in lavage fluid, with the addition of a new technique of gene expression profiling using macroarrays. The aim of the study was to use these macroarrays as a sensitive measurement of acute up- or down-regulation of genes that were taking place in the rat lung in response to the small instilled mass of DEP. DEP instillation caused a slight oedematous lung with no overt inflammation and ten out of a possible 207 (5%) rat stress genes were repeatedly changed in response to DEP instillation. Therefore, the conclusion from the macroarray analysis is in agreement with the conventional toxicology and suggest that DEP elicits a low bioreactive response in a healthy rat lung.