Mechanisms of particulate matter toxicity in neonatal and young adult rat lungs.

Particulate matter (PM*) has been associated with a variety of adverse health effects, primarily involving the cardiovascular and respiratory systems. Researchers continue to investigate biologic mechanisms that may explain how exposure to PM exacerbates or directly causes adverse effects. Particle composition may play a critical role in these effects. In this study we used a diffusion flame system to generate ultrafine iron, soot, and iron combined with soot particles and exposed young adult and neonatal rats to different compositions of these particles. Young adult rats inhaled all three PM compositions on three consecutive days for 6 hours per day. Exposure to soot PM at 250 microg/m3 or to iron PM at 57 microg/m3 demonstrated no adverse respiratory effects. However, we observed mild pulmonary stress when the iron concentration was increased to 90 microg/m3. The most striking effects resulted when the rats inhaled PM composed of iron (45 microg/m3) combined with soot particles (total mass 250 microg/m3). This type of exposure produced significant indicators of oxidative stress, signs of inflammation, and increases in the levels of cytochrome P450 isozymes in the lungs. Repeated three-day exposure of neonatal rats to soot and iron particles in the second and the fourth weeks of life produced significant oxidative stress (elevations in oxidized and reduced glutathione) and ferritin induction. Neonatal rats exposed to PM in the second week of life also had a subtle but significant cell proliferation reduction in the centriacinar regions of the lungs. These findings suggest that iron combined with soot PM can lead to changes in the respiratory tract not found with exposure to iron or soot PM alone at similar concentrations. Unique effects in the neonate suggest that age may play an important role in susceptibility to inhaled particles.