title: Low-dose treatment with polybrominated diphenyl ethers (PBDEs) induce altered characteristics in MCF-7 cells.
abstract: Polybrominated diphenyl ethers (PBDEs) are hydrophobic and persistent additive flame retardants that seemingly transfer into environmental compartments where they bioaccumulate i.e. in human biota. We examined the micronucleus-forming activities of low-dose PBDEs (congeners 47, 99, 153, 183 or 209) in MCF-7 cells along with their ability to modulate growth, cell biochemistry [by infrared (IR) microspectroscopy], clonogenic survival or quantitative expression of cytochrome P450 isoenzymes (CYP1A1, CYP1A2 and CYP1B1), cyclin-dependent kinase inhibitor 1A [CDKN1A (P21(WAF1/CIP1))], B-cell leukaemia/lymphoma-2 (BCL-2) and Bcl-2-associated X (BAX). Elevations in micronucleus formation were observed following treatment with 10(-12) to 10(-9) M PBDE concentrations despite the fact that less than one-fourth of the concentration of each test agent administered partitioned out of the media and into the incubating cells. However, low-dose treatment levels remained within the range of reported concentrations measured in UK serum samples collected in 2003. Clonogenic survival and gene expression was unaltered following 10(-12) to 10(-9) M PBDE treatment but significant (P < 0.05) elevations in growth kinetics were observed. Significant alterations in IR cell spectra were associated with treatments, and plotted clusters following principal component analysis highlighted these changes. Whether such in vitro effects point to an underlying ability of PBDEs to initiate and drive target-cell alterations in vivo now needs to be addressed.
authors.affiliation: Department of Environmental Science, Lancaster University Lancaster LA1 4YQ, UK.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Barber
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walsh
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hewitt
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Jones
authors.forename: Francis L
authors.initials: FL
authors.lastname: Martin
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced; D004355:Drug Stability; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015162:Micronucleus Tests / Q000379:methods; D015591:Microspectrophotometry / Q000379:methods; D010647:Phenyl Ethers / Q000633:toxicity*; D011075:Polybrominated Biphenyls / Q000633:toxicity*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C031538:phenyl ether