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

Abstract

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.

• Authors: Jau-Hong Lee, Hsu-Feng Lu, Der-Yean Wang, Dar-Ren Chen, Chin-Cheng Su, Yi-Shuan Chen, Jen-Hung Yang, Jing-Gung Chung
• Journal: Research communications in molecular pathology and pharmacology (Res Commun Mol Pathol Pharmacol) Vol. 115-116 Pg. 217-33 ( 2004) ISSN: 1078-0297 [Print] United States
• PMID: 17564319 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Hormonal
• Carcinogens
• DNA Adducts
• Fluorenes
• Receptors, Estrogen
• Tamoxifen
• 2-aminofluorene
• Arylamine N-Acetyltransferase

Topics

• Acetylation (drug effects)
• Antineoplastic Agents, Hormonal (pharmacology, therapeutic use)
• Arylamine N-Acetyltransferase (antagonists & inhibitors)
• Breast Neoplasms (drug therapy, enzymology, metabolism, pathology)
• Carcinogens (metabolism)
• Cell Line, Tumor
• DNA Adducts (antagonists & inhibitors, biosynthesis)
• Dose-Response Relationship, Drug
• Fluorenes (metabolism)
• Humans
• Kinetics
• Receptors, Estrogen (metabolism)
• Tamoxifen (pharmacology, therapeutic use)