Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis.
Within minutes of exposure of target cells to cytotoxic T lymphocytes, their nuclear DNA begins to be fragmented. This phenomenon precedes 51Cr release by at least an hour. DNA fragmentation occurs only when appropriately sensitized cytotoxic T cells are used and is not merely a result of cell death because killing of target cells by heating, freeze/thawing, or lysing with antibody and complement did not yield DNA fragments. Agarose gel electrophoresis of target cell DNA showed discrete multiples of an approximately 200-base-pair subunit, suggesting that fragmentation was the result of activation of a specific endonuclease. A similar pattern of DNA fragments is observed during glucocorticoid-induced killing of mouse thymocytes. The endonuclease in that case is inhibited by zinc ions, and we find that Zn2+ also inhibits DNA fragmentation and 51Cr release induced by cytotoxic T cells, suggesting a final common biochemical pathway for both types of cell death.
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004720:Endonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008970:Molecular Weight; D014176:Protein Biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
D004247:DNA; D004720:Endonucleases; D015032:Zinc