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PMID: 6312454 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis.

Duke RC, Chervenak R, Cohen JJ

Abstract

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.

MeSH Terms
Animals Cytotoxicity, Immunologic/drug effects DNA/metabolism Endonucleases/antagonists & inhibitors,metabolism Kinetics Mice Molecular Weight Protein Biosynthesis T-Lymphocytes, Cytotoxic/physiology Zinc/pharmacology
Chemicals
DNA Endonucleases Zinc
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Duke R C
Chervenak R
Cohen J J
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25 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1983-10-00
Pages
6361-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC394297
Subset
IM
Grants
NIAID NIH HHS · AI 11661 · United States
NINDS NIH HHS · NS 18461 · United States
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