The influence of butylated hydroxytoluene-induced cell proliferation on mouse lung damage after X rays or fission neutrons

To examine the relative importance of endothelial cells vs type II alveolar cells in the development of lung damage, we irradiated the lungs of mice with X rays either 2 or 6 days after treatment with butylated hydroxytoluene (BHT) and determined LD(50/180) values. LD(50/180) was 959 rad when no BHT was given, 269 rad when 2 days elapsed after BHT treatment, and 1445 rad at 6 days after BHT. The pattern of response was similar after fission neutron irradiation to the thorax. LD(50/180) after fission neutrons alone was 476 rad, but at 2 and 6 days after BHT, the LD(50/180) values were 98 and 575 rad, respectively. Clearly 2 days after BHT, when radiation injury to type II cells predominated, the sensitivity to both X rays and fission neutrons increased markedly, suggesting that injury to alveolar epithelial cells may be of primary importance in the development of lung damage in the mouse. Further, since certain antineoplastic drugs may induce a proliferative response in the lung similar to that produced by BHT, these data stress the fact that the timing between chemotherapy and radiation may be critical in the treatment of some cancers to avoid serious complications.