4.5 Article

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

Journal

JOURNAL OF CLINICAL LABORATORY ANALYSIS
Volume 31, Issue 6, Pages -

Publisher

WILEY
DOI: 10.1002/jcla.22130

Keywords

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

Funding

  1. Deanship of Scientific Research, King Saud University [RGP-VPP-175]

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BackgroundThe 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. MethodsThe 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 24h at 37 degrees C temperature. The binding characteristics of cancer auto-antibodies were assessed by direct binding and competitive inhibition ELISA. ResultsDNA 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. ConclusionThe HNE modified DNA presents unique epitopes which may be one of the factors for the autoantibody induction in cancer patients.

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