Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Lipid hydroperoxide-mediated DNA damage.

I A Blair1

  • 1Center for Cancer Pharmacology, University of Pennsylvania, 1254 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA. ian@spirit.gcrc.upenn.edu

Experimental Gerontology
|August 30, 2001
PubMed
Summary

Lipid hydroperoxides generate genotoxic aldehydes that damage DNA, forming mutagenic adducts. Advances in adduct analysis enable population studies on their role in cancer.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Regulation of lipid synthesis by the RNA helicase Mov10 controls Wnt5a production.

Oncogenesis·2015
Same author

Stable isotope dilution gas chromatography/mass spectrometry of prostaglandins and leukotrienes.

Biological trace element research·2013
Same author

Cyclooxygenase- and lipoxygenase-mediated DNA damage.

Cancer metastasis reviews·2011
Same author

Mass spectrometry in pharmaceutical analysis 1 *.

Journal of liposome research·2009
Same author

Oxidative DNA damage and cardiovascular disease.

Trends in cardiovascular medicine·2001
Same author

Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation.

Proceedings of the National Academy of Sciences of the United States of America·2001

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Toxicology

Background:

  • Lipid hydroperoxides (LHPs) are formed via reactive oxygen species and enzymatic pathways.
  • LHPs decompose into genotoxic alpha,beta-unsaturated aldehydes, including 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal.
  • These aldehydes can form DNA adducts, potentially leading to mutations.

Purpose of the Study:

  • To investigate the pathways of LHP decomposition into genotoxic aldehydes.
  • To characterize the DNA adducts formed by these aldehydes.
  • To explore the implications of these adducts in human health, particularly cancer.

Main Methods:

  • Analysis of LHP decomposition pathways.
  • Identification and characterization of DNA adducts using advanced analytical techniques.
  • Investigation of aldehyde-DNA interactions and adduct formation.
  • Exploration of the role of cyclooxygenase-2 in LHP and genotoxin production.

Main Results:

  • Two distinct pathways for LHP decomposition into genotoxic aldehydes were identified.
  • Specific DNA adducts, including etheno- and propano-adducts, were characterized from reactions with 4,5-epoxy-2(E)-decenal, 4-oxo-2-nonenal, and 4-hydroxy-2-nonenal.
  • Malondialdehyde, another genotoxic electrophile, is formed from LHPs and damages DNA.
  • Cyclooxygenase-2 upregulation by 4-hydroxy-2-nonenal creates a feedback loop for genotoxin production.

Conclusions:

  • Lipid hydroperoxide decomposition generates endogenous genotoxic DNA-damaging agents.
  • Characterization of these DNA adducts is advancing, enabling population dosimetry studies.
  • These studies are crucial for understanding the role of LHP-derived DNA adducts in mediating cancer.

Related Experiment Videos