8-oxo-7-8-dihydrodeoxyguanine and Breast-Neoplasms

8-oxo-7-8-dihydrodeoxyguanine has been researched along with Breast-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for 8-oxo-7-8-dihydrodeoxyguanine and Breast-Neoplasms

ArticleYear
Functional implications of antiestrogen induction of quinone reductase: inhibition of estrogen-induced deoxyribonucleic acid damage.
    Molecular endocrinology (Baltimore, Md.), 2003, Volume: 17, Issue:7

    Recent studies have shown that the antiestrogens tamoxifen and raloxifene may protect against breast cancer, presumably because of a blockade of estrogen receptor (ER)-mediated transcription. Another possible explanation is that antiestrogen-liganded ER transcriptionally induces genes that are protective against cancer. We previously reported that antiestrogen-liganded ERbeta transcriptionally activates the major detoxifying enzyme quinone reductase (QR) [NAD(P)H:quinone oxidoreductase]. It has been established that metabolites of estrogen, termed catecholestrogens, can form DNA adducts and cause oxidative DNA damage. We hypothesize that QR inhibits estrogen-induced DNA damage by detoxification of reactive catecholestrogens. We report here that physiological concentrations of 17beta-estradiol cause oxidative DNA damage, as measured by levels of 8- hydroxydeoxyguanine, in ER-positive MCF7 breast cancer cells, MDA-MB-231 breast cancer cells (ERalpha negative/ERbeta positive) and nontumorigenic MCF10A breast epithelial cells (very low ER), which is dependent on estrogen metabolism. Estrogen-induced 8-hydroxydeoxyguanine was inversely correlated to QR and ERbeta levels and was followed by downstream induction of the DNA repair enzyme XPA. Trans-hydroxytamoxifen, raloxifene, and the pure antiestrogen ICI-182,780 protected against estradiol-mediated damage in breast cancer cells containing ERbeta. This is most likely due to the ability of these antiestrogens to activate expression of QR via ERbeta. We conclude that up-regulation of QR, either by overexpression or induction by tamoxifen, can protect breast cells against oxidative DNA damage caused by estrogen metabolites, representing a possible novel mechanism of tamoxifen prevention against breast cancer.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Breast Neoplasms; DNA Damage; DNA Repair; DNA-Binding Proteins; Enzyme Activation; Epithelial Cells; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptor Modulators; Estrogens; Female; Fulvestrant; Guanine; Humans; NAD(P)H Dehydrogenase (Quinone); Oxidative Stress; Raloxifene Hydrochloride; Receptors, Estrogen; Tamoxifen; Tumor Cells, Cultured; Xeroderma Pigmentosum Group A Protein

2003