Preferential recognition of auto-antibodies against 4-hydroxynonenal modified DNA in the cancer patients

J Clin Lab Anal. 2017 Nov;31(6):e22130. doi: 10.1002/jcla.22130. Epub 2017 Jan 20.

Abstract

Background: The structural perturbations in DNA molecule may be caused by a break in a strand, a missing base from the backbone, or a chemically changed base. These alterations in DNA that occurs naturally can result from metabolic or hydrolytic processes. DNA damage plays a major role in the mutagenesis, carcinogenesis, aging and various other patho-physiological conditions. DNA damage can be induced through hydrolysis, exposure to reactive oxygen species (ROS) and other reactive carbonyl metabolites including 4-hydroxynonenal (HNE). 4-HNE is an important lipid peroxidation product which has been implicated in the mutagenesis and carcinogenesis processes.

Methods: The present study examines to probe the presence of auto-antibodies against 4-hydroxynonenal damaged DNA (HNE-DNA) in various cancer subjects. In this study, the purified calf thymus DNA was damaged by the action of 4-HNE. The DNA was incubated with 4-HNE for 24 h at 37°C temperature. The binding characteristics of cancer auto-antibodies were assessed by direct binding and competitive inhibition ELISA.

Results: DNA modifications produced hyperchromicity in UV spectrum and decreased fluorescence intensity. Cancer sera exhibited enhanced binding with the 4-HNE modified calf thymus DNA as compared to its native conformer. The 4-HNE modified DNA presents unique epitopes which may be one of the factors for the auto-antibody induction in cancer patients.

Conclusion: The HNE modified DNA presents unique epitopes which may be one of the factors for the autoantibody induction in cancer patients.

Keywords: DNA; 4-hydroxynonenal (HNE); auto-antibody; cancer; glycation.

MeSH terms

  • Aldehydes / pharmacology*
  • Animals
  • Antibodies, Neoplasm / immunology*
  • Antibodies, Neoplasm / metabolism
  • Autoantibodies / immunology*
  • Autoantibodies / metabolism
  • DNA / drug effects*
  • DNA / immunology*
  • DNA / metabolism
  • DNA Damage
  • Humans
  • Neoplasms / metabolism*

Substances

  • Aldehydes
  • Antibodies, Neoplasm
  • Autoantibodies
  • DNA
  • calf thymus DNA
  • 4-hydroxy-2-nonenal