Interaction of the photosensitization products of oestrone with DNA: comparison with the horseradish peroxidase catalyzed reaction.
The interaction with DNA of [4-14C]oestrone upon photosensitization with hematoporphyrin (HP) as a photosensitizer has been investigated. By means of Sephadex LH-20 gel filtration and extraction with dichloromethane it was found that, after irradiation (lambda greater than 425 nm) of a solution of HP, DNA and [4-14C]oestrone 21% of the radiolabel was associated with DNA. If DNA was added after irradiation 23% was bound to DNA, whereas 25% of the oestrone remained after photoreaction under the conditions applied. The binding occurs via the reactive 10 beta-hydroperoxy-1,4-estradien-3,17-dione, which is the only product after photosensitization of oestrone. The hydroperoxide has a strong interaction with DNA compared with that of other steroids. By repeated precipitation with 5 M NaCl and ethanol the association can be broken. It is reported, that binding of oestrone to protein induced by both photosensitization and horseradish peroxidase (HRPO)/H2O2 is irreversible, but that the amount of binding to DNA is dependent on the method of determination. However, neither the hydroperoxide nor its reduced product, a p-quinol, is intermediate or product in the HRPO catalyzed reaction of oestrogens. The tight association of the hydroperoxide product of oestrone with DNA, which may proceed via hydrogen bonding between the -OOH group and oxygen atoms of the backbone phosphate groups or of the furanose ring, might be a cause of chemical modification of DNA and of mutagenic effects.
D002384:Catalysis; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000528:radiation effects*; D004970:Estrone / Q000528:radiation effects*; D006415:Hematoporphyrins / Q000494:pharmacology; D006735:Horseradish Peroxidase; D010544:Peroxidases; D010777:Photochemistry
D006415:Hematoporphyrins; D004970:Estrone; D004247:DNA; D006735:Horseradish Peroxidase; D010544:Peroxidases