THE EXTENT AND PERSISTENCE OF BINDING TO RESPIRATORY MUCOSAL DNA BY INHALED TRITIATED PROPYLENE-OXIDE

In order to investigate some of the mechanisms underlying the carcinog enicity of inhaled propylene oxide (PO), the deposition and persistenc e of inhaled tritiated PO in the DNA of the nasal cavities, tracheae a nd lungs of rats were investigated. The results of dose/response expos ure protocols revealed clear gradients for binding throughout the resp iratory mucosa; the highest levels of binding were in the nasal mucosa and the lowest were in the lungs. Gradients became steeper as exposur e concentrations were lowered. The persistence studies revealed that b ound tritium declined in nasal mucosal DNA with apparent bi-exponentia l kinetics while clearance from the tracheal and pulmonary DNA was muc h slower and occurred with apparent mono-exponential kinetics. Consequ ently, although the initial levels of binding of inhaled PO are lower in the trachea and lungs than in the nasal cavity, the slow clearance of PO from the DNA in these organs could increase the chances of a mut ational event.