Antiserum detection of reactive carbonyl species-modified DNA in human colonocytes

Nalini Mistry, Ruth J. Bevan, Marcus S. Cooke, Mark D. Evans, Eugene P. Halligan, Damon Anthony Lowes, Karen Nichol, Joseph Lunec

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Polyunsaturated fats have been linked to occurrences of sporadic colon cancer. One possible cause may be degradation of polyunsaturated fats during cooking, resulting in multiple reactive carbonyl species (RCS) that can damage nuclear DNA and proteins, particularly in rapidly dividing colon crypt cells. This study describes a novel antiserum against RCS-modified DNA, with apparent order of reactivity to DNA modified with 4-hydroxy-trans-2-nonenal > glyoxal > acrolein > crotonaldehyde > malondialdehyde; some reactivity was also observed against conjugated Schiff base-type structures. Anti-(RCS-DNA) antiserum was successfully utilised to demonstrate formation of RCS-DNA in a human colon cell model, exposed to RCS insult derived from endogenous and exogenous lipid peroxidation sources. Further utilisation of the antiserum for immunohistochemical analysis confirmed RCS-modified DNA in crypt areas of `normal' colon tissue. These results fully support a potential role for dietary lipid peroxidation products in the development of sporadic colon cancer.

Original languageEnglish
Pages (from-to)344-353
Number of pages10
JournalFree Radical Research
Volume42
Issue number4
DOIs
Publication statusPublished - Apr 2008

Keywords

  • reactive carbonyl species
  • colon crypt cells
  • antiserum
  • colon cancer
  • lipid-peroxidation products
  • calf thymus DNA
  • in-vivo
  • immunohistochemical detection
  • chemical carcinogenesis
  • monoclonal-antibodies
  • deoxycytidine-glyoxal
  • diabetes-mellitus
  • oxidative stress
  • adducts
  • Reactive carbonyl species
  • antiserum

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