Mutagenesis, Vol. 17, No. 4, 345-352,
July 2002
© 2002 UK Environmental Mutagen Society/Oxford University Press
Genotoxic effects of oestrogens in breast cells detected by the micronucleus assay and the Comet assay
Department of Biological Sciences, IENS, Lancaster University, Lancaster LA1 4YQ, UK
Cumulative exposure to oestrogen has been linked to increased risk of breast cancer. Whilst oestrogens induce cancers in rodent bioassays it is unclear whether the mechanisms involved are genotoxic and/or epigenetic. The cytokinesis block micronucleus (CBMN) and the alkaline single cell-gel electrophoresis `Comet' assays were used to examine MCF-7 cells for chromosomal damage and DNA single-strand breaks (SSBs), respectively. The comet-forming activities of oestrogens were also tested in a 72 h primary culture of cells isolated from freshly expressed breast milk. Micronuclei (MN) were scored in 500 binucleate cells per treatment and SSBs were quantified by comet tail length (CTL) (µm). Effects on mitotic rate (per cent binucleate cells) and cell viability (per cent plating efficiency) were also assessed. ß-Oestradiol, oestrone and oestriol were tested for genotoxicity in the 10-10–10-4 M and 10-10–10-2 M concentration ranges in the CBMN and Comet assays, respectively. ß-Oestradiol, following 24 h treatment but not 120 h treatment, induced increases (up to 3-fold) in MN at a concentration of 10-9 M. Oestrone induced dose-related increases in MN (up to 5-fold) following both 24 and 120 h treatment, whereas oestriol appeared not to induce MN. All three oestrogens induced dose-related increases in per cent binucleate cells suggesting that they enhance mitotic rate. In the Comet assay both ß-oestradiol and oestrone induced dose-related increases in SSBs (up to 7-fold over control CTL) and were significantly comet-forming (P < 0.0001) at concentrations as low as 10-9 and 10-8 M, respectively, whereas oestriol was less genotoxic. All three oestrogens were significantly comet-forming (P < 0.0001) in a primary culture of breast milk cells, suggesting that they can damage the target cells from which breast cancers may eventually arise.
1 To whom correspondence should be addressed. Tel: +44 1524 593469; Fax: +44 1524 843854; Email: f.martin{at}lancaster.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Kabil, E. Silva, and A. Kortenkamp Estrogens and genomic instability in human breast cancer cells--involvement of Src/Raf/Erk signaling in micronucleus formation by estrogenic chemicals Carcinogenesis, October 1, 2008; 29(10): 1862 - 1868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Wasson, V. J. McKelvey-Martin, and C. S. Downes The use of the comet assay in the study of human nutrition and cancer Mutagenesis, May 1, 2008; 23(3): 153 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jiao, S. L. Allinson, M. J. Walsh, R. Hewitt, K. J. Cole, D. H. Phillips, and F. L. Martin Growth kinetics in MCF-7 cells modulate benzo[a]pyrene-induced CYP1A1 up-regulation Mutagenesis, March 1, 2007; 22(2): 111 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Barber, M. J. Walsh, R. Hewitt, K. C. Jones, and F. L. Martin Low-dose treatment with polybrominated diphenyl ethers (PBDEs) induce altered characteristics in MCF-7 cells Mutagenesis, September 1, 2006; 21(5): 351 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, K. W. Lee, F. L. Chan, S. Chen, and L. K. Leung The Red Wine Polyphenol Resveratrol Displays Bilevel Inhibition on Aromatase in Breast Cancer Cells Toxicol. Sci., July 1, 2006; 92(1): 71 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hammiche, M. J. German, R. Hewitt, H. M. Pollock, and F. L. Martin Monitoring Cell Cycle Distributions in MCF-7 Cells Using Near-Field Photothermal Microspectroscopy Biophys. J., May 1, 2005; 88(5): 3699 - 3706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. L. Martin and K. T. Semple Environmental health impacts: occurrence, exposure and significance, Lancaster University, UK, 9-10 September 2003 Mutagenesis, September 1, 2004; 19(5): 423 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. I. Kalantzi, R. Hewitt, K. J. Ford, L. Cooper, R. E. Alcock, G. O. Thomas, J. A. Morris, T. J. McMillan, K. C. Jones, and F. L. Martin Low dose induction of micronuclei by lindane Carcinogenesis, April 1, 2004; 25(4): 613 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Davis, S. Bhana, A. J. Shorrocks, and F. L. Martin Oestrogens induce G1 arrest in benzo[a]pyrene-treated MCF-7 breast cells whilst enhancing genotoxicity and clonogenic survival Mutagenesis, September 1, 2002; 17(5): 431 - 438. [Abstract] [Full Text] [PDF]
|
|