Delay of M-phase onset by aphidicolin can retain the nuclear localization of zinc and metallothionein in 3T3-L1 fibroblasts

The transient nuclear localization of metallothionein during cell growth an d differentiation may be related to the increased requirement of zinc for D NA synthesis, activation of metalloenzymes, and transcription factors. Trea tment of 3T3-L1 fibroblasts with aphidicolin, an inhibitor of nuclear DNA s ynthesis, caused a cell-cycle block at G1/S phase and a delay in the onset of M phase. This also resulted in the accumulation of both zinc and metallo thionein in the nucleus. After removal of aphidicolin, the cells rapidly re entered S phase, and during the G2/M phase of cell cycle both zinc and meta llothionein began to relocate to the cytoplasm. Delaying the onset of M pha se in 3T3-L1 cells could prevent the cytoplasmic relocation of metallothion ein. The nuclear translocation of both zinc and metallothionein during the cell cycle can be considered as a normal process and this may be a general mechanism in response to mitogenic signals, (C) 2000 Wiley-Liss, Inc.