DNA strand break and 8-hydroxyguanine formation induced by 2-hydroxyestradiol dispersed in liposomes

Abstract

DNA damage induced by estrogens dispersed in liposomes was investigated. 2-Hydroxyestradiol (2HOE 2) and 4-hydroxyestradiol (4HOE 2), but not estrone, estradiol-17β or estriol, caused strand break of plasmid DNA damage in the presence of ADP-Fe 3+. The catechol structure may be necessary for DNA damage. When DNA was incubated with 2HOE 2 for a long time (24 h), DNA damage was induced even at very low concentrations. Adding hydrogen peroxide markedly enhanced the sensitivity of DNA to the attack by 2HOE 2. Hydroxyl radical (HO ) scavengers strongly inhibited the 2HOE 2-induced DNA damage, and EDTA partially inhibited DNA damage. However, 2HOE 2 caused 8-hydroxyguanine formation from calf thymus DNA only in the presence of EDTA-Fe 3+, but not ADP-Fe 3+. In addition, deoxyribose, which is a detective molecule of HO , was not degraded by 2HOE 2 in the presence of ADP-Fe 3+. Upon adding EDTA 2HOE 2 rapidly degraded deoxyribose. These results suggest that DNA strand break caused by 2HOE 2 in the presence of ADP-Fe 3+ was due to ferryl ion rather than HO , whereas 8-hydroxyguanine (8HOG) induced by 2HOE 2 in the presence of EDTA-Fe 3+ was due to HO .