Age‐dependent changes in gene expression profiles of postnatally developing rat lungs exposed to nano‐size and micro‐size CuO particles

Abstract

We hypothesized that acute exposure of developing lungs to fine & ultrafine particles interferes with normal lung development. To test this hypothesis, we performed the following experiments. F‐344 rats [7, 14, >90 days(adult)] were exposed to intranasal instillations of nano‐, micro‐CuO particle suspensions or vehicle (PBS) alone. 48 hours post exposure we performed bronchoalveolar lavage (BAL) in some rats, and lung RNA extraction in others. BAL analyses showed consistent inflammatory response in 7 days‐old neonates and adult rats in response to both nano‐ and micro‐size CuO particles, but not to vehicle alone (PBS). 14‐days old rats did not respond to either size of CuO particles or PBS. Total RNA from unlavaged lungs were analyzed via rat RT2 Profiler PCR array. Both medkine‐heparin‐binding growth factor and c‐fos induced growth factor (also known as VEGF‐D) are up‐regulated in neonatal rats compared to adults, regardless of particle exposure. The pro‐inflammatory chemokine Cxcl2 is consistently up‐regulated in neonatal rats (7, 14 days‐old) comparing to same age PBS instilled group, when they are exposed to both nano‐ and micro‐CuO particles. In summary, PCR analysis in combination with BAL cell counts revealed age‐dependent lung inflammatory response to CuO particles; these methods can be used further to investigate the effects of particle exposure on the postnatal lung development at the molecular level.