ALTERATION OF ADENOSINE-TRIPHOSPHATE AND OTHER NUCLEOTIDES AFTER SUBLETHAL OXIDANT INJURY TO RAT TYPE-II ALVEOLAR EPITHELIAL-CELLS

The alveolar epithelial cells of the lower respiratory tract are conti nuously exposed to injurious agents, including oxygen radicals. The ty pe II alveolar epithelial cell is critically important to the normal f unction of the lung, because it is responsible for synthesis of surfac tant and other essential duties. The present investigation measured th e level of intracellular nucleotides and adenosine over time after exp osure of type II cells to sublethal concentrations of physiologically relevant oxidants, hydrogen peroxide and hypochlorous acid (HOCl), Ini tially, it was determined that 250 mu M HOCl or 250 mu M hydrogen pero xide could each cause sublethal injury to the type II cells after expo sure of up to 1 and 2 hours, respectively. After exposure to 250 mu M hydrogen peroxide, the intracellular levels of adenosine, adenosine di phosphate, and adenosine triphosphate all initially increased in the f irst 1 to 15 minutes, but subsequently decreased significantly, ultima tely reaching close to 40% below control levels. The level of adenosin e monophosphate remained significantly elevated throughout the exposur e until returning to control levels after 2 hours. Similar results occ urred after the type II cells were exposed to 250 mu M HOCl. This stud y demonstrates that adenosine triphosphate and other cellular nucleoti des and nucleosides were decreased in type II cells before lethal inju ry and subsequent cell death.