MP12 Organic, Metallic, Organometallic Pollutants
Monday, 14 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall

(BAR-1117-827879) Low-dose effects of polybrominated diphenyl ethers (PBDEs) in MCF-7 cells.

Barber, J¹, Hewitt, R¹, Jones, K¹, Martin, F¹, ¹ Lancaster University, Lancaster, Lancashire, UK

ABSTRACT- The release of PBDEs to the environment is increasingly being regarded as an environmental hazard. PBDEs can bioaccumulate and biomagnify, and increasing human-tissue concentrations have been detected in the last decade. We examined in MCF-7 breast cells the ability of four PBDE congeners (PBDEs-47, -153, -183 and -209) to elevate levels of chromosomal damage, measured as micronuclei in the cytokinesis-block micronucleus assay, compared to an appropriate vehicle control. These congeners are among the most abundant congeners found in human samples. Parallel experiments examining growth kinetics, clonogenic survival and quantitative expression, using real-time RT-PCR, of cytochrome P450 isoenzymes CYP1A1, CYP1A2 and CYP1B1 were also conducted. The ability of PBDEs to induce effects over a range of concentrations (10^-12 M to 10^-6 M) was explored. Marked elevations (2- to 5-fold) in micronucleus formation were observed following 24-h treatment with 10^-12 M, 10^-11 M, 10^-10 M or 10^-9 M PBDE congener; often not in a dose-response fashion but as a characteristic bell-shaped curve, the extent of PBDE-induced micronucleus formation appeared to be modulated between experiments by background levels i.e. the lower the background level the more profound the induced effect. While clonogenic survival was not altered, growth kinetics over 72-h incubation was up to 30% elevated. Reductions in CYP1A1, CYP1A2 and CYP1B1 expression occurred after 24-h PBDE treatment i.e. PBDE-153 reduced CYP1A1 expression to 10% compared to the calibrator control. Currently, the micronucleus origin (aneuploid Vs. clastogenic) using kinetochore antibody probes, and intra-cellular conformation changes using near-field micro-spectroscopy, are being investigated to further characterise these effects. Our results suggest that PBDEs are capable of inducing effects at low-dose levels that would be close to environmental exposures. Whether such effects in an oestrogen receptor-positive breast carcinoma immortalised cell line translate into a potential to modify susceptibility in relevant target cells remains to be explored.

Key words: PBDEs, micronuclei, MCF-7