Abstract Title:

Extensive chromosomal breaks are induced by tamoxifen and estrogen in DNA repair-deficient cells.

Abstract Source:

Cancer Res. 2004 May 1;64(9):3144-7. PMID: 15126352

Abstract Author(s):

Aki Mizutani, Takashi Okada, Shinya Shibutani, Eiichiro Sonoda, Helfrid Hochegger, Chikako Nishigori, Yoshiki Miyachi, Shunichi Takeda, Mitsuyoshi Yamazoe

Article Affiliation:

Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.


Tamoxifen (TAM) possesses antiestrogen activity and is widely used for the treatment or prevention of breast cancer. However, it is also carcinogenic in human uterus and rat liver, highlighting the profound complexity of its actions. To explore the molecular mechanisms of TAM-induced mutagenesis, we analyzed the effects of this drug on gene-disrupted chicken B lymphocyte (DT40) clones deficient in various DNA repair pathways. Rad18, Rev3, and Polkappa are involved in translesion DNA synthesis (TLS), which facilitates recovery from replication blocks on damaged template strands. DT40 cells deficient in TLS were found to be hypersensitive to TAM, exhibiting an increase in chromosomal breaks. Furthermore, these mutants were also hypersensitive to 4-hydroxyestradiol, a physiological metabolite of estrogen. These data suggest a contribution of TLS to the prevention of chromosomal breaks by TAM and estrogen, and they therefore indicate that such error-prone DNA synthesis underlies mutagenesis induced by these agents.

Study Type : Commentary

Print Options

Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & receive The Dark Side of Wheat Ebook

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

The Dark Side of Wheat

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2023 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.