Kinetic responses of murine sarcoma cells to radiation and hyperthermia in vivo and in vitro.

Cells of a solid mouse mammary sarcoma that can be cultured in vitro and which, upon inoculation, grow in vivo into new tumors, were exposed either in vivo or in vitro to doses of 300 or 600 rads of X-rays and/or to a temperature of 43 degrees for 1 hr. DNA histograms obtained with flow cytofluorometry were sampled at regular time intervals after treatments in order to obtain information on the cells' postexposure kinetics. X-irradiation of exponentially growing cells induced the expected G2 block; heat exposure caused cells to accumulate in S and G2. The sequential treatment (300 rads followed by 1 hr of hyperthermia) resulted in a mitotic delay that was longer than the sum of the delays of the individual treatments. The proliferative behavior of cycling cells in the tumor treated with a dose of X-rays was qualitatively similar to that seen for exponentially growing cells in vitro; however, marked differences were seen after 43 degrees exposure. The heat treatment of tumors in vivo caused a significant decrease in the tumor cell density as compared to the X-ray treatment alone. Sequential X-ray and heat treatment induced a higher fraction of cycling cells than that found in control tumors. However, X-ray or heat treatment alone caused no significant recruitment of resting cells into cycle 1 day after treatment. A model that permits estimation of the fraction of resting cells in a tumor is described.