[Study of the effect of antitumor agents on cell cycle traverse by flow cytometry]

The effect of antitumor agents on the cell cycle traverse of cultured FL cells, a monolayer culture line derived from human amnion, was investigated by flow cytometry (FCM) in combination with simultaneous determination of total cell number, viability, mitotic index and labeling index by [3H]TdR. The results obtained can be summarized as follows: Antimetabolites prolonged the duration of the S phase at a low dose, while at a high dose they decreased the rate of progression from the G1 to S phase, resulting in G1 and G1-S boundary accumulation. Partial synchronization by these agents was obtained through two different mechanisms. In vinca alkaloid-accumulated cells in the G2+M phase at 24h, mitotic index (MI) reached 20%, which was 10 to 20 times higher than that of control and most M-phase cells, which consisted of metaphase cells. Other cells in a tetraploid state were considered to be in the G2 phase or possibly G1 phase of the tetraploid cycle. Antibiotics generally accumulated cells in the G2 phase, but agents could be divided into two groups according to the degree of G2 accumulation. One group showed almost complete G2 accumulation, while the other showed only partial accumulation. The former group inhibited the progression of the S phase at a higher dose. Both groups completely inhibited the progression of the cell cycle at the highest dose. Alkylating agents only partially accumulated cells in the G2 phase at a low dose, showed prolongation of the S phase at a high dose, and inhibited the progression of the cell cycle at the highest dose, as with antibiotics. On the basis of these results, the application of these agents for treatment of cancer, especially leukemia, is discussed from a rational viewpoint.