Cell-free DNA is released from tumor cells upon cell death: a study of tissue cultures of tumor cell lines.

To determine the source of cell-free DNA detected in the serum of cancer patients, we monitored the release of cell-free DNA and tumor markers from tumor cell lines using the cell culture technique. During the first 6 days of cell culture, we found very low concentrations of DNA and a steady increase of the CA 125 released from the SK-BR3 tumor cell lines during cell growth. A sudden increase of cell-free DNA detected in the cell medium coincided with cell death. As the cells died, the concentration of cell-free DNA declined but the concentration of CA 125 increased. The sudden release of cell-free DNA observed upon cell death was also found on the cell cultures of additional tumor cell lines, including A549, RD, and SK-N-SH cells. It appears that the majority of cell-free DNA detected in the serum of cancer patients comes from tumor cells following cell death and cell necrosis. The concentration of cell-free DNA released is related to the number of dead cells, whereas that of the tumor marker CA 125 is associated with the presence of the total number of cells (dead or alive). Copyright 2003 Wiley-Liss, Inc.