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

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 [ 3 H]BaP–DNA binding assay, an increase of BaP–DNA adduct formation was observed with 17β-estradiol (E 2 )-induced ERα. Treatments of [ 3 H]BaP in conjunction with the E 2 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 E 2 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 E 2 . [ABSTRACT FROM AUTHOR]