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 [3H]BaP-DNA binding assay, an increase of BaP-DNA adduct formation was observed with 17beta-estradiol (E2)-induced ERalpha. 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 ERalpha expressed by E2.