Carcinogenesis, Vol 18, 2209-2215, Copyright © 1997 by Oxford University Press
EA Martin, P Carthew, IN White, RT Heydon, M Gaskell, RJ Mauthe, KW Turteltaub and LL Smith
Tamoxifen was administered to three strains of female mice (B6C3F1, C57BL/6
and DBA/2) in short- and long-term studies to determine their ability to
activate tamoxifen and cause hepatic DNA damage. 32P- Postlabelling of
liver DNA from mice treated for 4 days showed a group of major adducts that
increased in a dose-dependent manner and co- chromatographed with the major
adducts detected in rat liver. On cessation of dosing, the majority of
adducts were cleared within 3 days. Binding of [14C]tamoxifen to DNA
nucleotides was demonstrated by the use of accelerator mass spectrometry.
In long-term studies of 12 months to 2 years duration, dependent on strain,
tamoxifen was administered continuously in the diet to give a daily dose of
approximately 40 mg/kg. DNA adducts were detected after 3 months, although
the number of adducts decreased with time and by 2 years were not
detectable in the tamoxifen treated mice. None of the treated groups showed
a significantly increased incidence of liver tumours, with or without
phenobarbital promotion and there was no sustained liver cell
proliferation. Tamoxifen was detected in the mouse livers, but at levels 50
times lower than those reported in a comparable rat study. These results
suggest that, in contrast to the rat, tamoxifen is non-carcinogenic in mice
because it does not cause sufficient cumulative DNA damage, or act as a
promoter by causing cell proliferation.
ARTICLES
Investigation of the formation and accumulation of liver DNA adducts in mice chronically exposed to tamoxifen
MRC Toxicology Unit, Hodgkin Building, University of Leicester, UK.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Brown Is tamoxifen a genotoxic carcinogen in women? Mutagenesis, September 1, 2009; 24(5): 391 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Y. Kim, N. Suzuki, Y. R. S. Laxmi, and S. Shibutani INEFFICIENT REPAIR OF TAMOXIFEN-DNA ADDUCTS IN RATS AND MICE Drug Metab. Dispos., February 1, 2006; 34(2): 311 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Colleoni, S. Li, R. D. Gelber, A. S. Coates, M. Castiglione-Gertsch, K. N. Price, J. Lindtner, C.-M. Rudenstam, D. Crivellari, J. Collins, et al. Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor Ann. Onc., May 1, 2005; 16(5): 716 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Martin, K. Brown, M. Gaskell, F. Al-Azzawi, R. C. Garner, D. J. Boocock, E. Mattock, D. W. Pring, K. Dingley, K. W. Turteltaub, et al. Tamoxifen DNA Damage Detected in Human Endometrium Using Accelerator Mass Spectrometry Cancer Res., December 1, 2003; 63(23): 8461 - 8465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Schild, R. L. Divi, F. A. Beland, M. I. Churchwell, D. R. Doerge, G. Gamboa da Costa, M. M. Marques, and M. C. Poirier Formation of Tamoxifen-DNA Adducts in Multiple Organs of Adult Female Cynomolgus Monkeys Dosed with Tamoxifen for 30 Days Cancer Res., September 15, 2003; 63(18): 5999 - 6003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shibutani, N. Suzuki, Y. R. S. Laxmi, L. J. Schild, R. L. Divi, A. P. Grollman, and M. C. Poirier Identification of Tamoxifen-DNA Adducts in Monkeys Treated with Tamoxifen Cancer Res., August 1, 2003; 63(15): 4402 - 4406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Poirier and L. J. Schild The Genotoxicity of Tamoxifen: Extent and Consequences, Kona, Hawaii, January 23, 2003 Mutagenesis, July 1, 2003; 18(4): 395 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Phillips Understanding the genotoxicity of tamoxifen? Carcinogenesis, June 1, 2001; 22(6): 839 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Boocock, J. L. Maggs, K. Brown, I. N.H. White, and B.K. Park Major inter-species differences in the rates of O-sulphonation and O-glucuronylation of {alpha}-hydroxytamoxifen in vitro: a metabolic disparity protecting human liver from the formation of tamoxifen-DNA adducts Carcinogenesis, October 1, 2000; 21(10): 1851 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. N.H. White The tamoxifen dilemma Carcinogenesis, July 1, 1999; 20(7): 1153 - 1160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Boocock, J. L. Maggs, I. N.H. White, and B. K. Park {alpha}-Hydroxytamoxifen, a genotoxic metabolite of tamoxifen in the rat: identification and quantification in vivo and in vitro Carcinogenesis, January 1, 1999; 20(1): 153 - 160. [Abstract] [Full Text] [PDF]
|
|