Abstract
Evidence is presented which suggests the existence of at least two growth control points in cultured mammalian cells. These controls are in โparallelโ rather than in โseries.โ It is suggested that in normal and some transformed cells the controls are coupled while in SV40 transformed cells and tumor cells they are uncoupled. One control is revealed by cytochalasin B (CB) treatment since in normal and some kinds of transformed cells, CB treatment results in the accumulation or the arrest of cells in G1. In this case, the control is normal or coupled. In DNA tumor virus transformed cells and many cultured tumor cells (excluding human glioblastomas) CB does not arrest cells although it prevents cytoplasmic division. Such cells continue DNA synthesis and nuclear division and become highly multinucleated. The effects of CB are not concentration dependent. Here the control is defective or uncoupled. Another control is revealed by caffeine treatment. Again, normal and some types of transformed cells are accumulated in G1 following caffeine treatment, while SV40 transformed cells and tumor cells continue DNA synthesis unabated. The effects of caffeine in arresting cells are concentration dependent. Similarly the control point revealed by caffeine is coupled in normal cells and altered or uncoupled in some SV40 transformed and tumor cells. Although CB and caffeine do not inhibit DNA synthesis in tumor and SV40 transformed cells when administered separately, they cause G1 accumulation when administered in combination. This observation can be explained by the possibility that some transformed cells can utilize alternate or parallel mechanisms to progress through G1 when one mechanism is blocked (CB or caffeine). When both are blocked the cells become arrested in G1. The human glioblastomas are unique among the cultured human tumors thus far examined since they are partially arrested by CB. However they are like other human tumors in that caffeine does not significantly affect DNA synthesis.