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Title: Tamoxifen DNA damage detected in human endometrium using accelerator mass spectrometry.
Authors: Martin, Elizabeth A.
Brown, Karen
Gaskell, Margaret
Al-Azzawi, Farook
Garner, R. Colin
Boocock, David J.
Mattock, Elizabeth
Pring, David W.
Dingley, Karen
Turteltaub, Kenneth W.
Smith, Lewis L.
White, Ian N.H.
First Published: 1-Dec-2003
Publisher: American Association for Cancer Research
Citation: Cancer Research, 2003, 63 (23), pp. 8461-8465
Abstract: This study was aimed to establish whether tamoxifen binds irreversibly to uterine DNA when given to women. Patients were given a single therapeutic dose of [14C]tamoxifen citrate orally (20 mg, 0.37 or 1.85 MBq) ∼18 h prior to hysterectomy or breast surgery. Nonmalignant uterine tissue was separated into myometrium and endometrium. DNA and protein were isolated and bound radiolabel determined by the sensitive technique of accelerator mass spectrometry. Levels of irreversible DNA binding of tamoxifen in the endometrium of treated patients were 237 ± 77 adducts/1012 nucleotides (mean ± SE, n = 10). In myometrial tissues, a similar extent of DNA binding was detected (492 ± 112 adducts/1012 nucleotides). Binding of tamoxifen to endometrial and myometrial proteins was 10 ± 3 and 20 ± 4 fmol/mg, respectively. In breast tissue, sufficient DNA could not be extracted but protein binding was an order of magnitude higher than that seen with endometrial proteins (358 ± 81 fmol/mg). These results demonstrate that after oral administration, tamoxifen forms adducts in human uterine DNA but at low numbers relative to those previously reported in women after long-term tamoxifen treatment where levels, when detected, ranged from 15,000 to 130,000 adducts/1012 nucleotides. Our findings support the hypothesis that the low level of DNA adducts in human uterus is unlikely to be involved with endometrial cancer development.
ISSN: 0008-5472
Type: Article
Description: This paper was published as Cancer Research, 2003, 63 (23), pp. 8461-8465. It is available from or from the journal website at
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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