Interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA and DNA-damaging molecules and its impact on DNA repair activity

Abstract

1,4-dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. Interaction of some 1,4-DHP with DNA was recently reported. AV-153-Na, an antimutagenic and DNA-repair-enhancing compound appeared to be able to interact with DNA by intercalation.The aim of the current study was to characterize DNA's capacity for the binding of AV-153-Na, and using different approaches, to test intracellular distribution of the compound, to test the ability of the compound to scavenge peroxynitrite and hydroxyl radical and to assess the ability of the compound to modify the activity of DNA repair enzymes.The DNA binding activity of AV-153-Na was determined by means of fluorescence assay. Laser confocal scanning fluorescence microscopy demonstrated that within the cells AV-153-Na was found mostly in the cytoplasm; however, a stain in nucleolus was also detected. Binding to cytoplasmic structures might occur due to high affinity of the compound to protein, revealed by fluorescence spectroscopy titration and circular dichroism. Activation of DNA repair enzymes after binding to DNA appears to be the basis for the antimutagenic effects of AV-153-Na.