Changes in nuclear distribution of large tumor antigen correlate with the proliferative activity of simian virus 40-transformed cells

A correlation between intranuclear distribution of large tumor antigen (T-ag) and proliferative activity in Simian virus 40 (SV40)-transformed cells has been established. Nuclear T-ag was cytochemically detected by the immunoperoxidase reaction. Cell populations with a high growth rate displayed a heterogeneous pattern with patches of positive reaction surrounded by large and irregular negative areas. By contrast, cell populations with a low growth rate presented a rather homogeneous distribution of nuclear T-ag with a finely granular positive reaction all over the nucleus, excluding nucleolus-like areas. The latter pattern was also observed in cells that had been inhibited from traversing S phase. In this case, the heterogeneous distribution of T-ag within the nucleus was recovered once the cells were allowed to proceed again through S phase, or through G2 phase. Highly condensed chromatin in mitotic chromosomes appeared to exclude T-ag fully as early as in prophase. Then, nuclear distribution of T-ag changes throughout the cell cycle, thus suggesting it might be a cell cycle-dependent event. Interestingly, thymidine-labeled cells from cultures with a high growth rate presented a heterogeneous distribution of autoradiographic grains. Regardless of their mechanism(s) of origin, T-ag-enriched areas might correspond to nuclear sites where a specific function, such as DNA synthesis, is being carried out.