Changes in DNA content during in vitro transformation of mouse salivary gland epithelium.

DNA content was measured in single cells in situ during the in vitro development of neoplastic transformation in epithelial cells from mouse salivary glands. The earliest change in DNA content was found in stage III of the transformation process (a preneoplastic stage). In foci of these cells, the percentage of tetraploid (4C) cells was 30--60% compared with the starting tissue and early primary cultures, which were diploid. The stage III foci eventually gave rise to subtetraploid tumorigenic cell lines. The studies suggested that during in vitro development of neoplastic transformation in salivary gland epithelium, tetraploids were generated that then underwent a period of chromosome instability and loss. Evidence was also presented that a similar mechanism may be operating in transformation of salivary gland epithelium in vivo. A possible mechanism for transformation on the basis of chromosome imbalance was discussed.