Nucleosomal fragments in serum may directly reflect cell-mediated cytotoxic activity in vivo

In in vitro experiments the activity of cytotoxic T-cells and natural killer cells has been shown to cause nuclear DNA fragmentation leading to the release of nucleosomal multimers from the target cells. These multimers form a ladder-like pattern with a periodicity of approximately 200 bp during gel electrophoresis. The objective of the present study was to show the relevance of the presence of these nucleosomal multimers in vivo during diseases that show cell-mediated cytotoxicity. Nucleosomal multimers (n greater than 5) could be detected using nick translation followed by electrophoresis in a series of sera of a chimpanzee infected with hepatitis A virus and in sera drawn from several hepatitis B patients. The multimers were present during periods expected to show an increased activity of cell-mediated cytotoxicity in the liver. During these periods the injury of the liver cells was also mirrored by the classical parameter, the release of a specific liver enzyme into the serum. The liver enzyme activity in the serum and the detection of the nucleosomal multimers did not completely overlap, however. It is postulated that the proposed nick translation assay is useful as a simple diagnostic test for cell-mediated cytotoxicity since it reflects this activity under different in vivo situations.