CHANGES OF CELL PROLIFERATION CHARACTERISTICS IN A RAT RHABDOMYOSARCOMA BEFORE AND AFTER X-IRRADIATION

Proliferation characteristics of cells in an experimental rhabdomyosarcoma, transplantable in an inbred strain of WAG/Rij rats, have been studied for unirradiated and irradiated tumours by autoradiography. The cell cycle parameters have been compared with equivalent data for the same strain of cells cultured in vitro. Fractions of labelled cells and labelled mitoses were counted as a function of time after pulse labelling with tritiated thymidine. The changes in proliferation characteristics of cells in the tumours are discussed in relation to the volume variations of the tumours before and after irradiation. The results show that the tumour growth rate decreases with increasing tumour volume. The volume doubling time Ta is 2·5 days for a tumour volume V of 0·3 cm3 and Ta=6 days at V=1·5 cm3. This decrease is due to a change in cell cycle parameters, including a lengthening of the mean cell cycle from 20 to 25 hr in parts of the tumour corresponding to a decrease in the rate of production of new cells, as well as to an increase in the rate of cell loss. The growth fraction in small tumours is equal to 0·42 and in the large tumours to 0·29. After irradiation with 2000 rad X-rays of tumours with a volume of 1·5 cm3, tumour volume decreases and on the tenth day it reaches a value of about 0·75 of the pre-irradiation volume. However, the fraction of cells which after this radiation dose have retained the capacity for unlimited proliferation is equal to only 0·008. Measurements of cell cycle parameters on the fourth day after irradiation showed that cells present in the tumour at that time proliferate with a shorter cell cycle time of about 12 hr. Cell loss at four days after irradiation exceeded cell production however and caused the volume to decrease. Cell cycle parameters of the same cell line of rhabdomyosarcoma cells cultured in vitro showed that in small clones containing about 80 cells, the mean cell cycle time is 16 hr, the growth fraction is 1·0 and no cell loss occurs, whereas in large clones containing about 1200 cells, the mean cell cycle time is 16·5 hr, the growth fraction is 0·39 and the cell loss factor is small. © 1969.