Formation of DNA-protein cross-links in mammalian cells by levuglandin E2

Levuglandin E2 (LGE2), a rearrangement product derived from the prostaglandin endoperoxide, PGH2, causes repair-resistant DNA-protein cross-links and cell death (LD50 = 230 nM) in V79 Chinese hamster lung fibroblasts. The half-life for sequestration of LGE2 by covalent binding to cellular nucleophil...

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Bibliographic Details
Published in:Biochemistry (Easton) 1993-04, Vol.32 (15), p.4090-4097
Main Authors: Murthi, Krishna K, Friedman, Libby R, Oleinick, Nancy L, Salomon, Robert G
Format: Article
Language:English
Subjects:
Ageing, cell death
Animals
Biological and medical sciences
Cell Line
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Cell physiology
Cell Survival - drug effects
Clone Cells
Cross-Linking Reagents - pharmacology
DNA - metabolism
Dose-Response Relationship, Drug
Fundamental and applied biological sciences. Psychology
Hydrogen-Ion Concentration
Kinetics
Lung
Molecular and cellular biology
Nuclear Proteins - metabolism
Prostaglandins E - pharmacology
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Summary:Levuglandin E2 (LGE2), a rearrangement product derived from the prostaglandin endoperoxide, PGH2, causes repair-resistant DNA-protein cross-links and cell death (LD50 = 230 nM) in V79 Chinese hamster lung fibroblasts. The half-life for sequestration of LGE2 by covalent binding to cellular nucleophiles is at least an hour for 10 microM LG. This suggests that the in vivo production and distribution of free LGs should be measurable on this time scale. Following removal of the LGE2 and the return of the cultures to normal growth medium, additional DNA-protein cross-links continued to form over the ensuing 6-24 h. The results suggest that LG adducts to DNA or protein are not repaired, but react further at sites on protein or DNA in close proximity to the initial adducts, forming cross-links in a slow phase of the process.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00066a034