The effect of age on crystalline silica-induced pulmonary toxicity-aged rats
The effect, if any, of age on the pulmonary toxicity induced by Min-U-Sil 5 crystalline silica exposure was investigated in rats. As part of the study, the changes in global gene expression profiles in the blood and lungs of the animals were determined.  To conduct these studies, to determine if age influences the pulmonary response to crystalline silica exposure, two different age groups of healthy, male F344 rats were used.  In this study the old age group of rats (12 months old at the time of exposure) was exposed to either air or crystalline silica (Min-U-Sil 5) (15 mg/m3, 6 hours/day, 5 days) by whole body inhalation. The old age group of rats simulates a group of workers who would be 45 to 50 years old.  At two crystalline silica post-exposure time periods (1-day and 6-months) animals were euthanized and pulmonary inflammatory, cytotoxic, and oxidant responses were determined.  Analysis of bronchoalveolar lavage parameters of toxicity such as oxidant generation and inflammation revealed significant changes in pulmonary toxicity in the crystalline silica exposed rats compared with the time-matched, air exposed control rats. The blood gene expression profiles showed only minimal changes, at both the time points, in the crystalline silica exposed rats compared with the controls. Specifically, no genes were significantly differentially expressed (fold change >1.5 and FDR p<0.05) in the one-day post-exposure group and only 6 genes were significantly differentially expressed in the 6-month post-exposure group. However, the lung gene expression profiles showed substantial changes in the crystalline silica exposed animals at both one-day and 6-month post-exposure.  Specifically, there were a total of 325 genes significantly differentially expressed (fold change >1.5 and FDR p<0.05) at the one-day post-exposure group and 3348 genes significantly differentially expressed at the 6-month post-exposure. The data obtained from the present study demonstrated that crystalline silica inhalation exposure, under the conditions employed in the present study, resulted in significant changes in lung toxicity parameters and lung gene expression profile in the rats at both 1-day and 6-month post-exposure. Overall design: Rats were exposed by whole-body inhalation to filtered air or crystalline silica (Min-U-Sil 5) (15 mg/m3, 6 hours/day, 5 days).  At post exposure time intervals of 1- day and 6-months, rats were euthanized, and lung and blood samples collected.