Lee Jau-Hong, Lu Hsu-Feng, Wang Der-Yean, Chen Dar-Ren, Su Chin-Cheng, Chen Yi-Shuan, Yang Jen-Hung, Chung Jing-Gung
Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan, ROC.
Res Commun Mol Pathol Pharmacol. 2004;115-116:217-33.
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.
他莫昔芬被用于确定N - 乙酰转移酶（NAT）活性及2 - 氨基芴（2 - AF）-DNA加合物形成在人乳腺癌细胞中的作用。乳腺癌细胞根据雌激素受体状态分为两组，即雌激素受体阳性（ER(+)）和雌激素受体阴性（ER(-)）。ER(+)乳腺癌细胞中2 - AF - DNA加合物的形成量分别为2.58±0.39 pmol加合物/毫克DNA，ER(-)乳腺癌细胞中为2.74±0.46 pmol加合物/毫克DNA。与1微摩尔他莫昔芬共同处理分别使ER(+)和ER(-)细胞中的DNA加合物形成抑制高达65%和61%。他莫昔芬对ER(+)和ER(-)细胞间DNA加合物形成的抑制作用无显著差异。人乳腺癌细胞中N - 乙酰转移酶活性的结果被他莫昔芬以剂量依赖性方式抑制。他莫昔芬分别抑制ER(+)和ER(-)细胞中50.0%和42.8%的Km以及58.2%和35.6%的Vmax。基于对N - 乙酰转移酶活性的动力学研究，他莫昔芬在乙酰化反应中起非竞争性作用。本研究表明，无论雌激素受体状态如何，他莫昔芬不仅抑制人乳腺癌细胞中的NAT活性，还抑制DNA加合物的形成。这些发现可能为他莫昔芬在乳腺癌中有化学预防作用提供线索。
