Effects of activated macrophages on tumor target cells in discrete phases of the cell cycle.

Studies were performed in vitro to examine the cytostatic properties of activated macrophages on tumor cells in various phases of the cell cycle. EMT-6 target cells were synchronized in the M phase by mitotic selection techniquese and placed in culture. As the population of target cells proceeded to various discrete phases of the cell cycle in a high degree of synchrony, these cells were challenged with normal macrophages or activated macrophages from Corynebacterium parvum-treated mice, and their subsequent ability to synthesize DNA and undergo mitosis was observed. Regardless of when normal macrophages were added, they had little effect on the target cells. In contrast, target cells in the M or G1 phase at the time of challenge with activated macrophages failed to undergo DNA synthesis (S phase), and their subsequent mitosis was inhibited. Similarly, when tumor cells were in the early or mid-S phase at the time of challenge, DNA synthesis was markedly inhibited, and mitosis was blocked. When activated macrophages were added to EMT-6 cells failed to undergo the impending phase of mitosis. These results suggest that the inhibition of target cell DNA synthesis by activated macrophages is not a prerequisite for the ability of these effector cells to block target cell multiplication.