Preferential recognition of catechol-estrogen modified DNA by circulating autoantibodies in cancer patients.
Catecholestrogens [4-hydroxyestradiol (4-OHE(2))] have been implicated in human carcinogenesis, although the mechanism remains unestablished. In this study pUC 18 plasmid DNA was modified with 4-OHE(2) and nitric oxide (NO). The modification induced in native DNA exhibited hyperchromicity, single strand breaks, damage to restriction sites, modification of bases, decrease in Tm and change in ellipticity. Modified DNA was found to be highly immunogenic in experimental animal, eliciting high titer antibodies. Circulating cancer autoantibodies showed preferable recognition of 4-OHE(2)-NO-DNA over native form (p < 0.001) and the oxidative epitopes on the DNA isolates from cancer patients were immunochemically detected by using experimentally induced anti-4-OHE(2)-NO-DNA antibodies as a probe. Preferential recognition of 4-OHE(2)-NO-DNA by cancer autoantibodies coupled with enhanced binding of induced antibodies to DNA isolated from cancer patients is an indicative of oxidative stress induced DNA damage in cancer. Possible involvement of unique epitopes on modified DNA in cancer autoantibody induction has been suggested.
Department of Biochemistry, Faculty of Medicine, JN Medical College, AMU, Aligarh 202002, India. wahidalikhan@rediffmail.com
Wahid Ali
WA
Khan
Moinuddin
Safia
S
Habib
D000328:Adult; D000974:Antibodies, Antinuclear / Q000737:chemistry / Q000276:immunology*; D016022:Case-Control Studies; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D004926:Escherichia coli / Q000737:chemistry; D002393:Estrogens, Catechol / Q000737:chemistry*; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide / Q000737:chemistry; D009690:Nucleic Acid Conformation / Q000187:drug effects; D018384:Oxidative Stress; D010957:Plasmids / Q000737:chemistry
D000974:Antibodies, Antinuclear; D004273:DNA, Neoplasm; D000939:Epitopes; D002393:Estrogens, Catechol; D009569:Nitric Oxide; C014036:4-hydroxyestradiol