The hypothesis was tested that continuous
hyperoxia would enhance the development of lung
tumors in mice. In strain A/J mice treated with a single dose of
urethan (1000 mg/kg) and exposed to 70% O2 for 16 wk, an average of 5
tumors per lung developed, whereas in animals kept in air, an average of 20
tumors per lung was found. When the animals were returned to air after
oxygen exposure, it was found that a difference of 15
tumors per lung between the two groups persisted up to 1 yr later, indicating that O2 was tumoricidal. The shortest duration of O2 exposure to be effective was 4 wk, and delay of O2 exposure up to 12 wk after
urethan still was effective in reducing the number of developing
tumors. Histopathology showed that continued exposure to 70% O2 produced some
hyperplasia of the bronchiolar epithelium and only very discrete changes in the pulmonary parenchyma. Analysis of cell proliferation patterns with a continuous [3H]
thymidine labeling technique showed a persistent high cell labeling in the bronchiolar epithelium and a temporary increase in alveolar wall cell labeling. Chronic
hyperoxia failed to alter the activities of pulmonary
superoxide dismutase or
glucose-6-phosphate dehydrogenase.
Ornithine decarboxylase, on the other hand, was increased as long as the animals remained exposed to
oxygen. It was concluded that
hyperoxia kills developing
tumor cells in mouse lung.