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Depression: 21st Century Solutions + The Dark Side of Wheat

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.

Abstract:

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

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Sayer Ji
Founder of GreenMedInfo.com

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Depression: 21st Century Solutions + The Dark Side of Wheat

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