SELECTIVE KILLING INDUCED BY AN INHIBITOR OF N-LINKED GLYCOSYLATION

Treatment with a low dose (0.5 mug/ml) of tunicamycin (an inhibitor of N-linked glycosylation) blocked the cell cycle progression of both no rmal Balb/c 3T3 cells (A31) and their SV40-transformed derivatives (SV A31) specifically in early G1 (0-3 h after mitosis). Upon release afte r an 8-h treatment the A31 cells returned to the cell cycle via a 9-h recovery phase, indicating that they were arrested in Go. The A31 cell s were fully viable after this treatment. In contrast, the postmitotic SVA31 cells, which were unable to arrest in G0, did not divide after the removal of tunicamycin. Instead, these cells died but this did not occur until 22-34 h after release from the treatment. SVA31 cells tha t had passed the postmitotic phase of G1 survived during the parental generation and divided normally. However, a large portion of these cel ls died during the next cycle, and in total during a 48-h period appro ximately 50% of the cells were killed as a consequence of an 8-h expos ure to tunicamycin. In contrast, treatment with inhibitors of protein synthesis and HMG CoA reductase activity as well as inhibitors of modi fication of N-linked oligosaccharide chains did not result in cell dea th