Proliferative response of type 2 lung epithelial cells after X rays and fission neutrons

A method has been developed for study of the type 2 epithelial cell population in situ in BALB/c mouse lung by measurement of the uptake of [¹⁴C]thymidine into DNA of pulmonary cells after stimulation with the antioxidant butylated hydroxytoluene (BHT). Within 2 days of BHT injection there was a marked increase in total lung weight, total labeling index, and [¹⁴C]thymidine incorporation. Autoradiographic procedures revealed that the proliferative response 2 days after BHT was due primarily to type 2 alveolar cells, which comprised 80% of the [³H]thymidine-labeled lung cells at that time. Therefore it appeared that this system might provide a means of monitoring the type 2 cell population after irradiation. Radiation modified the BHT-induced proliferative response in a dose-dependent manner, but it did not alter the relative number of labeled cell types in the lung. Thus 2 days after mice were treated with irradiation and BHT, when the proliferative response was due to type 2 cells, [¹⁴C]-thymidine incorporation and DNA levels in the lung were determined after various doses of 300-kVp X rays and fission neutrons. Dose-response curves were generated from these data, and the radiation response was characterized by the reciprocal of the slope of the exponential region of the curves, designated D₀(PF). When irradiation was followed immediately by the proliferative stimulus BHT, the D₀(PF) values were 120 rad for 300-kVp X rays and 60 rad for fission neutrons. Based on these D₀(PF) values, relative biological effectiveness of 2.0 was obtained.