Influence of Transitory, as Compared with Permanent, High-Altitude Exposure on the Pathogenesis of Spontaneous and X-ray-induced Neoplasms in RF/Un Mice1

This study was undertaken to investigate the mechanisms of effects of high altitude on spontaneous and irradiationinduced neoplasia, with particular reference to the influence of the time and duration of high-altitude exposure on the pathogenesis of such growths. Female RF/Un mice exposed to 150 R whole-body Xor sham irradiation at 10 weeks of age were subsequently housed at high (4540 m) or low (150 m) altitude for various lengths of time. In such animals, the overall incidence of neoplasms was increased and the life-span was decreased by irradiation, irrespective of alti tude; animals residing at high altitude into old age showed further life shortening with a decrease in the overall incidence of neoplasms, in addition to polycythemia, im pairment of weight gain, lymphoid atrophy, decrease in the incidence of lymphoreticular tumors, and increase in the incidence of pulmonary neoplasms, angiomatoid, telangiectatic, and thrombotic lesions, myocarditis, and pneumonia. In animals residing at high altitude for only 3 months after irradiation, the effects of high altitude were drastically reduced; however, the induction of granulocytic leukemia in such animals was enhanced, perhaps through hypoxiainduced stimulation of hemopoietic stem cells which had not yet recovered from irradiation. Since the long-term effects of high-altitude exposure prolonged into old age were not reproduced by transitory exposure early in adult life, the effects may have been mediated largely through influences on late stages in the pathogensis of neoplasms and other age-related lesions, as opposed to early stages in their development.