Early Chromosomal Changes in SV₄₀-Infected Human Fibroblast Cultures

The relationship between growth-rate changes and chromosomal changes during serial passage of adult human fibroblasts was examined. The phase of rapid growth in vitro is followed by a phase of progressively declining growth rate and finally, by a phase of cellular degeneration. The declining growth phase is associated with a rising level of tetraploid metaphases. In the degenerating phase, the tetraploid level increases further and aneuploid cells first appear. SV₄₀-infection of cultured fibroblasts in the declining growth phase results in rapid and extensive chromosome alterations in the first few days following infection. Chromosome alterations in cultures 1 to 7 days after infection were examined in detail. There is a sharp increase in tetraploid metaphases due, in part, to endoreduplication. An increased frequency of breaks was seen within 2 days, and dicentric chromosomes were common by the 4th day. The normally occurring secondary constrictions became more pronounced and a member of the 6-X group, thought to be the late-replicating X chromosome, appeared to be preferentially lost. Telomeric associations involving most members of the complement were frequently encountered; evidence is presented indicating that these associations can lead to the formation of dicentric chromosomes. The telomeres of the long arm of chromosome 4 (or 5) in this cell strain were most often involved in dicentric formation. The rapid response of the several areas of relatively inert chromatin suggests an early viral effect on this material. The relationship, if any, between these early chromosome changes and the changes in the physiology of viral transformed cells remains to be elucidated.