Overexpression of mos oncogene product in Swiss 3T3 cells induces apoptosis preferentially during S-phase.

When Swiss 3T3 cells are acutely infected with Moloney murine sarcoma virus containing the v-mos oncogene, 90% of the cells round up and detach from the monolayer (floating cells) and express high levels of v-Mos. The majority of the floating cells are generated between 30 and 70 h post infection when the cellular level of Mos reaches approximately 0.1% of the total protein. Seventy percent of the floating cells exclude trypan blue but are growth arrested with 2C or 4C DNA content, whereas the remaining floating cells with < 2C DNA content, are dead or dying, and show characteristic apoptotic phenotypes. The apoptotic cells are most likely generated from cells in S-phase since these cells are absent from the viable floating cell population and the percentage of cells with < 2C DNA approximated the expected S-phase fraction of logarithmically growing cells. In addition, 5'-bromo-2'-deoxyuridine-labeling studies showed that approximately 50% of the floating cells with typical apoptotic phenotypes were metabolically-labelled with the drug. These analyses show that cell populations in different stages of the cell cycle are differently affected by high levels of v-Mos expression and cells in S-phase appear to be uniquely sensitive and undergo apoptosis.