IMPACT OF ESTRADIOL AND PROGESTERONE ON ANTIOXIDANT ACTIVITY IN NORMAL HUMAN BREAST EPITHELIAL-CELLS IN CULTURE

The risk of developing breast cancer increases after long term use of oestrogen and progestagen, and carcinogenesis in the breast is partly due to oxidative damage to DNA bases. Therefore, we studied the effect s of 17 beta-oestradiol and progesterone on the antioxidative status a nd the vulnerability to oxidative stress exhibited by normal human bre ast epithelial cells in culture. After exposure to hydrogen peroxide, cells grown with oestradiol alone or with both oestradiol and progeste rone showed significantly decreased viability compared to cells grown in medium without added hormones. There was, however, no difference in hydrogen peroxide degradation rate between controls and hormone treat ed cultures. When desferrioxamine was added, the viability increased a nd the hydrogen peroxide degradation rate decreased. The levels of sev eral antioxidants were altered in cells grown in the presence of oestr adiol and progesterone: the concentrations of glutathione reductase an d catalase decreased significantly while the levels of glutathione per oxidase and reduced glutathione did not change. The alterations in enz yme activity and cell vulnerability were more pronounced in cultures t reated with a combination of oestradiol and progesterone. We conclude that the redox balance in the cultured normal human breast epithelial cells was altered by treatment with oestradiol and progesterone, and t hat this change led to the increased death of cells subsequently expos ed to hydrogen peroxide. This effect may have implications for sex hor mone dependent diseases of the breast.