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.
Lee
Jau-Hong
JH
Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan, ROC. jauhong@yahoo.com
Lu
Hsu-Feng
HF
Wang
Der-Yean
DY
Chen
Dar-Ren
DR
Su
Chin-Cheng
CC
Chen
Yi-Shuan
YS
Yang
Jen-Hung
JH
Chung
Jing-Gung
JG
D000107:Acetylation / Q000187:drug effects; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002273:Carcinogens / Q000378:metabolism; D045744:Cell Line, Tumor; D018736:DNA Adducts / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D002273:Carcinogens; D018736:DNA Adducts; D005449:Fluorenes; D011960:Receptors, Estrogen; D013629:Tamoxifen; C012177:2-aminofluorene; D001191:Arylamine N-Acetyltransferase