The prolongation of mitotic stages in SV40-transformed vs nontransformed human fibroblast cells.

Early studies on the duration of mitotic stages and on metaphase-to-prophase ratios in a number of normal and neoplastic cells indicated that the process of mitosis becomes altered during the course of oncogenesis. However, the nature of these changes and their effects on each of the mitotic stages are still unclear. With the use of time lapse cinemicrography, we have compared the durations of mitotic stages of SV40/WI-38 and SV40/WI-26 cells to those of their normal counterparts and to other nontransformed human fibroblasts. We also examined the relative frequencies of the individual mitotic stages in fixed preparations of WI-38 and SV40/WI-38 cells. The data show that metaphase durations are increased in the transformed cells and as much as 3-4.7-fold in SV40/WI-38 cells compared to WI-38 and other nontransformed cells. Other stages are also prolonged though to lesser degrees. These findings suggest that increased metaphase/prophase ratios observed in many tumors are due to increases in duration of metaphase rather than to shorter prophases, and that increased mitotic indices commonly observed in malignant tumors and sometimes used as an index of growth rate are at least in part due to the prolongation of mitotic stages.