In vivo growth kinetics of P388 and L1210 leukemias

The P388 lymphocytic leukemia and the L1210 lymphoid leukemia are used as test systems for putative cytotoxic drugs. These leukemias are also used to investigate the perturbation of cell cycle progression of various chemical compounds in more detail. There is little information on the normal growth kinetics in vivo of these leukemias. In the present report we therefore present the results from growth kinetic studies of P388 and L1210 leukemic cells growing in ascites form in mice. We used 3H-TdR autoradiography, DNA flow cytometry and the stathmokinetic method. During exponential growth both leukemias showed a growth fraction of unity. Whereas no significant cell loss was observed during the early growth phase of P388 cells, cell loss was indicated by a discrepancy between potential and actual doubling times during exponential growth of L1210 cells. During the phase of growth retardation, the proportion of G1 and G2 cells increased at the expence of a reduced S phase fraction in the P388 leukemia, whereas only small changes in cell cycle distributions were seen with time after inoculation of L1210 cells. An increasing discrepancy in the reduction of the S phase fraction and the 3H-TdRLI was seen in the P388 cells with time after inoculation. Thus, a majority of P388 cells with S phase DNA content were unlabelled during the late phase of growth restriction, indicating resting cells in S phase. A good correlation was found between the 3H-TdR LI and S phase fraction throughout the life history of L1210 cells, revealing considerable differences in in vivo growth kinetics between the two leukemias. Such differences should be considered when evaluating test results.