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Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831
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.
1 Research sponsored by the Office of Health and Environmental Research, United States Department of Energy, under Contract DE-AC05-840R21400 with the Martin Marietta Energy Systems, Inc.
2 Recipient of support under an appointment to the Laboratory Cooperative Postgraduate Research Training Program administered by the Oak Ridge Associated Universitites for the United States Department of Energy. Present address: The Procter and Gamble Co., Cincinnati, OH.
3 Guest investigator, Department of Pathology, University of Tennessee Memorial Research Center, Knoxville, TN. Present address: University of Arkansas for the Medical Sciences, Little Rock, AR.
Received 9/ 9/85. Revised 11/25/85. Accepted 12/16/85.
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