Abstract
Catecholestrogens [4-hydroxyestradiol (4-OHE2)] have been implicated in human carcinogenesis, although the mechanism remains unestablished. In this study pUC 18 plasmid DNA was modified with 4-OHE2 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-OHE2-NO-DNA over native form (p < 0.001) and the oxidative epitopes on the DNA isolates from cancer patients were immuno-chemically detected by using experimentally induced anti-4-OHE2-NO-DNA antibodies as a probe. Preferential recognition of 4-OHE2-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. (C) 2012 Elsevier Masson SAS. All rights reserved.