Tobacco smoke exposure exacerbated crystalline silica-induced lung toxicity in rats

Smoking may modify the lung response to silica exposure including cancer
and silicosis. Nevertheless, the precise role of exposure to tobacco smoke
(TS) on the lung response to crystalline silica (CS) exposure and the
underlying mechanisms need further clarification. The objectives of the
present study were to determine the role of TS on lung response to CS
exposure and the underlying mechanism(s). Male Fischer 344 rats were
exposed by inhalation to air, CS (15 mg/m3, 6 hrs/day, 5 days), TS (80
mg/m3, 3 hrs/day, twice weekly, 6 months), or CS (15 mg/m3, 6 hrs/day, 5
days) followed by TS (80 mg/m3, 3 hrs/day, twice weekly, 6 months). The
rats were euthanized 6 months and 3 weeks following initiation of the
first exposure and the lung response was assessed. Silica exposure
resulted in significant lung toxicity as evidenced by lung histological
changes, enhanced neutrophil infiltration, increased LDH levels, enhanced
oxidant production, and increased cytokine levels.  The TS
exposure alone had only a minimal effect on these toxicity parameters.
However, the combined exposure to TS and CS exacerbated the lung response,
compared to TS or CS exposure alone. Global gene expression changes in the
lungs correlated with the lung toxicity severity. Bioinformatic analysis
of the gene expression data demonstrated significant enrichment in
functions, pathways, and networks relevant to the response to silica
exposure which correlated with the lung toxicity detected. Collectively
our data demonstrated an exacerbation of CS-induced lung toxicity by TS
exposure and the molecular mechanisms underlying the exacerbated toxicity.