Reduced Lung Cell Proliferation Following Short-Term Exposure to Ultrafine Soot and Iron Particles in Neonatal Rats: Key to Impaired Lung Growth?

Abstract

Particulate matter (PM) has been associated with a variety of negative health outcomes in children involving the respiratory system and early development. However, the precise mechanisms to explain how exposure to airborne particles may cause adverse effects in children are unknown. To study their influence on early postnatal development, a simple, laminar diffusion flame was used to generate an aerosol of soot and iron particles in the size range of 10 to 50 nm. Exposure of 10-day-old rat pups to soot and iron particles was for 6 h/day for 3 days. The lungs were examined following a single injection of bromodeoxyuridine (BrdU) 2 h prior to necropsy. Neonatal rats exposed to these particles demonstrated no effect on the rate of cell proliferation within terminal bronchioles or the general lung parenchyma. In contrast, within those regions arising immediately beyond the terminal bronchioles (defined as the proximal alveolar region), the rate of cell proliferation was significantly reduced compared with filtered air controls. These findings strongly suggest exposure to airborne particles during early neonatal life has significant direct effects on lung growth by altering cell division within critical sites of the respiratory tract during periods of rapid postnatal development. Such effects may result in altered growth in the respiratory system that may be associated with lifelong consequences.

The authors thank Dale Uyeminami for the operation of the diffusion flame system and oversight of all animal care and management. This research was supported by National Institutes of Health grants ES00628, ES05707, ES11634, and RR00169, Health Effects Institute contract 97-8, National Science Foundation grant 0137922, U.S. Environmental Protection Agency STAR grants 827995 and 829215, and the National Center for Electron Microscopy at Lawrence Berkeley National Laboratory under the U.S. Department of Energy contract DE-AC-03 76SF00098. Although the research described in this article has been funded in part by the U.S. Environmental Protection Agency, it has not been subjected to the agency's required peer and policy review and therefore does not necessarily reflect the views of the agency and no official endorsement should be inferred.