Jiao, Haiyan and Allinson, Sarah L. and Walsh, Michael J. and Hewitt, Rebecca and Cole, Kathy J. and Phillips, David H. and Martin, Francis L. (2007) Growth kinetics in MCF-7 cells modulate benzo[a]pyrene-induced CYP1A1 up-regulation. Mutagenesis, 22 (2). pp. 111-116. ISSN 1464-3804
Full text not available from this repository.Abstract
Pro-carcinogens, such as benzo[a]pyrene (B[a]P), that are exogenous ligands of the aromatic hydrocarbon receptor may influence the susceptibility of target-cell populations through the up-regulation of cytochrome P450 (CYP) mixed function oxidases. We examined whether the growth kinetics of MCF-7 cells might determine the level of up-regulation of CYP1A1, CYP1A2 or CYP1B1 by B[a]P, and whether this could then influence subsequent levels of DNA damage. Cell cultures manipulated to be G0/G1-phase concentrated, S-phase concentrated or G2/M-phase concentrated were treated with B[a]P and the expression levels of CYP1A1, CYP1A2, CYP1B1, cyclin-dependent kinase inhibitor 1A [CDKN1A (P21WAF1/CIP1)], B-cell leukaemia/lymphoma-2 (BCL-2), and Bcl-2-associated X levels were determined. Levels of DNA damage were measured as DNA single-strand breaks (SSBs) by the alkaline single-cell gel electrophoresis (comet) assay or as DNA adducts by 32P-postlabelling analysis. B[a]P-induced up-regulation of CYP1A1 was >100-fold in S-phase-concentrated cells, but in G0/G1-phase- or G2/M-phase-concentrated cultures up-regulation occurred to a significantly lower extent. Consistent with this, B[a]P-treated S-phase-concentrated cultures exhibited markedly up-regulated P21WAF1/CIP1, higher levels of dose-related increases in DNA SSBs, and increased DNA adduct levels presumably as a result of CYP1A1-mediated activation of B[a]P to B[a]P-diol-epoxide compared with the cultures enriched for the other cell cycle phases. Growth kinetics in vitro may be an important predeterminant of susceptibility to an exogenous pro-carcinogen in short-term test systems and these findings have important implications when extrapolating such results to a particular target-cell population in vivo.
| Item Type: | Article |
|---|---|
| Journal or Publication Title: | Mutagenesis |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Departments: | Faculty of Science and Technology > Lancaster Environment Centre Faculty of Health and Medicine > Biomedical & Life Sciences |
| ID Code: | 10151 |
| Deposited By: | Dr Sarah Allinson |
| Deposited On: | 08 Jul 2008 13:11 |
| Refereed?: | Yes |
| Published?: | Published |
| Last Modified: | 26 Jul 2012 14:44 |
| Identification Number: | |
| URI: | http://eprints.lancs.ac.uk/id/eprint/10151 |
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