Stimulation of DNA synthesis in lungs of hamsters tolerant to nitrogen dioxide.

Nitrogen idoxide (NO2) is both edematogenic and cytotoxic to the lung. Preexposure to NO2 protects against mortality from formation of excessive pulmonary edema (tolerance) and, depending on the preexposure schedule, may or may not protect against the cytotoxic effects of NO2 in the lung. Measurement of DNA synthesis in hamster lung was used to study the question of whether the more subtle cytological injury induced by NO2 is mediated by a system which also exhibits tolerance. It was found that when hamsters are preexposured daily to 10 ppm NO2, they develop tolerance against normally lethal concentrations of NO2; are protected against further cytological injury from 10 ppmNO2; but are not protected from the cytotoxic effects of NO2 greater than 10 ppm. Animals exposed weekly to 10 ppm NO2 are not protected from further cytotological injury induced byweekly exposures to 10 ppm NO2, but do develop tolerance against lethal concentrations of NO2. Thus the data indicate that induction of tolerance to NO2 does not necessarily protect the cell populations of the lung from the cytotoxic effects of NO2.