Tamoxifen DNA Damage Detected in Human Endometrium Using Accelerator Mass Spectrometry

Elizabeth A. Martin, Karen Brown, Margaret Gaskell, Farook Al-Azzawi, R. Colin Garner, David J. Boocock, Elizabeth Mattock, David W. Pring, Karen Dingley, Ken W Turteltaub, Lewis L. Smith, Ian N H White

Research output: Contribution to journalArticle

64 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)8461-8465
Number of pages5
JournalCancer Research
Volume63
Issue number23
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Tamoxifen
Endometrium
DNA Damage
Mass Spectrometry
DNA
Nucleotides
Breast
Proteins
DNA Adducts
Myometrium
Endometrial Neoplasms
Hysterectomy
Protein Binding
Uterus
Oral Administration
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Martin, E. A., Brown, K., Gaskell, M., Al-Azzawi, F., Garner, R. C., Boocock, D. J., ... White, I. N. H. (2003). Tamoxifen DNA Damage Detected in Human Endometrium Using Accelerator Mass Spectrometry. Cancer Research, 63(23), 8461-8465.

Tamoxifen DNA Damage Detected in Human Endometrium Using Accelerator Mass Spectrometry. / Martin, Elizabeth A.; Brown, Karen; Gaskell, Margaret; Al-Azzawi, Farook; Garner, R. Colin; Boocock, David J.; Mattock, Elizabeth; Pring, David W.; Dingley, Karen; Turteltaub, Ken W; Smith, Lewis L.; White, Ian N H.

In: Cancer Research, Vol. 63, No. 23, 01.12.2003, p. 8461-8465.

Research output: Contribution to journalArticle

Martin, EA, Brown, K, Gaskell, M, Al-Azzawi, F, Garner, RC, Boocock, DJ, Mattock, E, Pring, DW, Dingley, K, Turteltaub, KW, Smith, LL & White, INH 2003, 'Tamoxifen DNA Damage Detected in Human Endometrium Using Accelerator Mass Spectrometry', Cancer Research, vol. 63, no. 23, pp. 8461-8465.
Martin EA, Brown K, Gaskell M, Al-Azzawi F, Garner RC, Boocock DJ et al. Tamoxifen DNA Damage Detected in Human Endometrium Using Accelerator Mass Spectrometry. Cancer Research. 2003 Dec 1;63(23):8461-8465.
Martin, Elizabeth A. ; Brown, Karen ; Gaskell, Margaret ; Al-Azzawi, Farook ; Garner, R. Colin ; Boocock, David J. ; Mattock, Elizabeth ; Pring, David W. ; Dingley, Karen ; Turteltaub, Ken W ; Smith, Lewis L. ; White, Ian N H. / Tamoxifen DNA Damage Detected in Human Endometrium Using Accelerator Mass Spectrometry. In: Cancer Research. 2003 ; Vol. 63, No. 23. pp. 8461-8465.
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