Carcinogenesis Advance Access originally published online on December 19, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 25, No. 4, 613-622,
April 2004
Carcinogenesis vol.25 no.4 © Oxford University Press 2004; all rights reserved.
CARCINOGENESIS |
Low dose induction of micronuclei by lindane
1 Department of Environmental Science and 2 Department of Biological Sciences, IENS, Lancaster University, Lancaster LA1 4YQ, UK, 3 Department of Histopathology, Royal Lancaster Infirmary, Ashton Road, Lancaster LA1 4RP, UK and 4 Environmental Research Solutions, Ghyll Cottage, Mill Side, Witherslack, Near Grange-over-Sands, Cumbria LA11 6SG, UK
Environmental contaminants possessing hormonal activity have long been suspected of playing a role in cancer causation. What is unclear is whether such agents elicit their effects through genotoxic and/or epigenetic mechanisms. 
-Hexachlorocyclohexane (-HCH, lindane) was tested in the 10-12–10-4 M range. Chromosomal damage in MCF-7 breast cells and PC-3 prostate cells was assessed using the cytokinesis block micronucleus assay. Micronuclei (MNi) were scored in 1000 binucleate cells per treatment. Cell viability and cell cycle kinetics were also assessed, along with immunocytochemical and quantitative gene expression analyses of CDKN1A (P21WAF1/CIP1), BCL-2 and BAX. Following 24 h treatment, lindane (10-12–10-10 M) induced increases (up to 5-fold) in MNi in both cell lines. Increases in MNi occurred in the absence of DNA single-strand breaks or cytotoxicity and, compared with benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, at low concentrations. Lindane induced more MNi than the 
or ß stereoisomers of HCH. Low dose lindane (10-12–10-10 M) significantly elevated the percentage of MCF-7 cells staining positive for Bcl-2 and of PC-3 cells staining positive for Bax. Only high dose lindane (10-4 M) disrupted cell cycle kinetics with increases in percentage of cells in G1 and decreases in percentage of cells in G2/M. Despite a comparable high dose lindane induction of cell cycle arrest, marked increases in expression of P21WAF1/CIP1 were observed only in MCF-7 cells, although in PC-3 cells a significant increase (P < 0.0005) in the percentage of cells staining positive for p21Waf1/Cip1 was seen. These results suggest that ‘environmental’ concentrations of lindane can induce a number of subtle alterations in breast and prostate cells in the absence of cytotoxicity.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. N. Singh, H. F. Stringfellow, S. E. Taylor, K. M. Ashton, M. Ahmad, K. R. Abdo, O. M.A. El-Agnaf, P. L. Martin-Hirsch, and F. L. Martin Elevated expression of CYP1A1 and {gamma}-SYNUCLEIN in human ectopic (ovarian) endometriosis compared with eutopic endometrium Mol. Hum. Reprod., November 1, 2008; 14(11): 655 - 663. [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]
|
|
|
|
 |
|
 N. Ledirac, S. Antherieu, A. D. d'Uby, J.-C. Caron, and R. Rahmani Effects of Organochlorine Insecticides on MAP Kinase Pathways in Human HaCaT Keratinocytes: Key Role of Reactive Oxygen Species Toxicol. Sci., August 1, 2005; 86(2): 444 - 452. [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]
|
|