Effects of tamoxifen on DNA adduct formation and arylamines N-acetyltransferase activity in human breast cancer cells.

Tamoxifen was used to determine the effects of N-acetyltransferase(NAT) activity and 2-aminofluorene (2-AF)-DNA adduct formation in human breast cancer cells. Breast cancer cells were categorized into two groups based on the status of estrogen receptor, ER (+) and ER (-). 2-AF-DNA adduct formations in breast cancer cells are 2.58 +/- 0.39 pmol adduct/mg DNA for ER (+) and 2.74 +/- 0.46 pmol adduct/mg DNA for ER (-), respectively. Co-treatment with 1 microM tamoxifen inhibited DNA-adduct formations up to 65% in ER (+) and 61% in ER (-), respectively. The inhibition of Tamoxifen on DNA adduct formation between ER (+) and ER (-) cell was not significantly different. The results of the N-acetyltransferase activity in human breast cancer cells were inhibited by tamoxifen in a dose dependent manner. Tamoxifen inhibited 50.0% and 42.8% of Km in ER (+) and ER (-), 58.2% and 35.6% of Vmax, respectively. Based on the kinetic study of N-acetyltransferase activity, tamoxifen plays a non-competitive role in the acetylation reaction. This study demonstrates that tamoxifen inhibited not only NAT activity but also DNA-adduct formation in human breast cancer cells, regardless of the status of estrogen receptor. These findings could provide a clue that tamoxifen has chemoprevention effects in breast cancer.

Citation

Jau-Hong Lee, Hsu-Feng Lu, Der-Yean Wang, Dar-Ren Chen, Chin-Cheng Su, Yi-Shuan Chen, Jen-Hung Yang, Jing-Gung Chung. Effects of tamoxifen on DNA adduct formation and arylamines N-acetyltransferase activity in human breast cancer cells. Research communications in molecular pathology and pharmacology. 2004;115-116:217-33

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PMID: 17564319

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