Effects of X rays and fission neutrons on an induced proliferative response in lung type 2 epithelial cells

The recovery of the proliferative response induced by butylated hydroxytoluene (BHT) was evaluated in the type 2 epithelial cell population of BALB/c mouse lung after X ray or fission neutron irradiation. Previous autoradiographic studies revealed that the proliferative changes in the lung 2 days after BHT administration were due primarily to type 2 alveolar cells. When given immediately before BHT, radiation caused a dose-dependent decrease in the BHT-induced proliferative response, measured by [¹⁴C]thymidine incorporation into DNA and by labeling studies. When the time between irradiation and BHT injection was lengthened, the proliferative response gradually returned in a dose-dependent manner. 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 curve, designated D₀(PF). Two types of recovery processes were investigated. (i) When the BHT stimulus after a single dose of X rays was delayed, the D₀ (PF) increased from 120 (immediate BHT stimulation) to 360 rad at 2 days and to 580 rad by 14 days. After fission neutron irradiation, the D₀ (PF) value was 60 rad at both 0 (immediate BHT stimulation) and 2 days but increased to 345 rad by 14 days. (ii) Split-dose studies revealed a decline in the prolifeative response when the interval between 100-rad fractions was less than 12 hr. After that time, the proliferative response returned to control values (2 days) and by 7 days had almost doubled.