Effect of Estrogen Receptor (ER) on Benzo[a]pyrene–DNA Adduct Formation in Human Breast Cancer Cells

Abstract

To investigate the role of estrogen and estrogen receptor (ER) during benzo[a]pyrene (BaP) carcinogenesis, BaP–DNA adduct formation, and DNA synthesis were examined in ER-positive, MCF-7, and ER-negative, MDA-MB-231, human breast cancer cell lines. In MCF-7, the ER-positive human breast cancer cell line, treated with BaP, the formation of BaP–DNA adducts and DNA synthesis were inhibited in a concentration-responsive manner, but there was no change in MDA-MB-231, the ER-negative cell line. In the [3H]BaP–DNA binding assay, an increase of BaP–DNA adduct formation was observed with 17β-estradiol (E2)-induced ERα. Treatments of [3H]BaP in conjunction with the E2 induced a 2.1-fold increase in BaP–DNA adduct over BaP alone in the ER-positive MCF-7 cell line. In addition, the antiestrogen tamoxifen (TAM) blocked this effect by 82%, while E2 produced no change in the ER-negative MDA-MB-231 cell line. These observations suggest that the increased formation of BaP–DNA adducts may be mediated through the ERα expressed by E2. This research was supported by the Brain Korea 21 project 2003.