TI:  How Far Does Ozone Penetrate Into the Pulmonary Air/Tissue 
     Boundary Before it Reacts?

DT:  September 10, 1991

AU:  William A. Pryor, Biodynamics Institute, Louisiana State 
     University, Baton Rouge, LA 70803-1800, USA

SO:  Free Radical Biology $ Medicine, Vol. 12,pp 83-88, 1992

AB:  A simple method is suggested for calculating the time it 
     takes ozone to traverse a biological region, such as a 
     bilayer or a cell, and comparing this time to the half-life 
     of ozone within that region.  For a bilayer the calculations 
     suggest that most of the ozone reacts within a bilayer, but 
     a fraction may exit unreacted.  For the lung lining fluid 
     layer (LLFL), the calculations show that ozone cannot cross 
     this layer without reacting where the LLFL is thicker than 
     about 0.1 um.  However, since the LLFL varies from 20 to 0.1 
     um in thickness with patchy areas in the lower airways that 
     are virtually uncovered, some ozone could reach underlying 
     cells, particularly in the lower airways.  For cells (such 
     as alveolar type 1 epithelial cells), the calculations show 
     that ozone reacts within the cell too rapidly to pass 
     through and exit unreacted from the other side.

     These calculations have implication for ozone toxicity.  In 
     vivo, the toxicity of ozone is suggested to result from the 
     effects of a cascade of products that are produced in the 
     reactions of ozone with primary target molecules that lie 
     close to the air/tissue boundary.  These products, which 
     have a lower reactivity and longer lifetime than ozone 
     itself, can transmit the effects of ozone beyond the 
     air/tissue interface.  The variation in thickness of the 
     LLFL may modulate the species causing damage to the cells 
     below it.  In the lower airways, where the LLFL is thin and 
     patchy, more cellular damage may be caused by ozone itself; 
     in the upper airways where the LLFL is thicker, secondary 
     products (such as aldehydes and hydrogen peroxide) may cause 
     most of the damage.  In vitro studies must be designed in an 
     attempt to model the lung physiology.  For example, if cells 
     in culture are studied, and if the cells are exposed to 
     ozone while under a supporting medium solution that contains 
     ozone-reactive substances, then the cells may be damaged by 
     products that are formed in the reactions of ozone with the 
     cell medium rather than by ozone itself.