Tolerance and cross-tolerance using NO2 and O2. I. Toxicology and biochemistry

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Abstract
Rats exposed to 85% O2 develop tolerance to subsequent exposures to 100% O2. This adaptive change may be due to either nonspecific responses of the lung to injury, or to specific adaptations uniquely stimulated by O2 or its subsequent metabolic products. To evaluate whether or not any of the changes occurring in the lungs of these animals are unique to O2 exposures, tolerance for O2 was compared with that of another potent oxidant, NO2. Tolerance and cross-tolerance between these 2 gases was tested, and assays were performed for enzymes necessary for cellular repair and protection against some of the toxic products of O2 metabolism. Exposure to 100% O2 for 72 h or 75 ppm NO2 for 6 h is lethal for control rats. Rats continuously exposed to 85% O2 for 5 days developed tolerance to 100% O2 and were partially cross-tolerant to exposures to 75 ppm NO2. Rats exposed to 25 ppm NO2 for 6 h/day became tolerant to 75 ppm NO2 after 2 or more days, but did not demonstrate significant cross-tolerance to exposure to 100% O2. When evaluated on a per whole-lung basis, cuprozinc superoxide dismutase, mangano superoxide dismutase, glucose-6-phosphate dehydrogenase (G6PD) and catalase were significantly increased after 5 days'' exposure to 85% O2. Preexposure to 25 ppm NO2 led to a small increase in G6PD and catalase caused a 41% increase in cytochrome oxidase and failed to significantly change the activity of either of the superoxide dismutases. The induction of increased superoxide activity by O2 exposure is postulated to be a specific defense adaptation for O2 and may be part of the reason why NO2 preexposures failed to give significant cross-protection against 100% O2.

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