Transformation of diploid human lung fibroblasts with oncogene ras increases the frequency of abnormal mitoses.

The human oncogene ras p21 was transfected into human lung fibroblast WI-38 diploid cells. All of the clones that were isolated (n = 36), exhibited rapid growth and transformed morphology which was ascertained by both transmission and scanning electron microscopy as extensive formations of microvilli on the plasma membrane, marked distortion of the nuclear membrane and increased number of pinocytotic vesicles in the cortical cytoplasm. The frequency of abnormal metaphases rose from 15% in parental WI-38 cells to 35.5-48.4% in all ten clones examined. Lagging chromosomes in prometaphase represented 42.1-69.4% of the total abnormal mitoses followed in frequency by 3-group metaphase and C-metaphase. All transformed cells were aneuploid. These data provide evidence for the association between cellular transformation with oncogenic ras and elevated abnormal mitoses in human cells.