Polybrominated diphenyl ether (PBDE) congeners are constituents of flame retardants, and there is growing concern regarding their persistence, bioaccumulation, and toxicity. We collected breast milk samples between late 2001 and early 2003 from 54 U.K.-resident mothers. Of these, 27 originated from southeast England (London), and the other 27 originated from northwest England (Lancaster). Analysis of milk-fat extracts by gas chromatography–mass spectrometry was performed to determine the levels of 15 PBDE congeners, 15 polychlorinated biphenyl (PCB) congeners, and other selected chlorinated compounds. PCB and organochlorine (OC) levels in southeast samples were consistently higher, and significant differences (p < 0.05) were observed. ∑PBDE levels ranged from 0.3 to 69 ng/g lipid (geometric mean, 6.6 ng/g), and PBDE-47 was the most abundant congener. ∑PCB levels ranged from 26 to 530 ng/g lipid (geometric mean, 150 ng/g) and were composed mainly of PCB-153 (26%), PCB-138 (20%), and PCB-180 (13%). OC levels for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p′-DDT) and its metabolites (∑DDX) ranged from 24 to 2,300 ng/g lipid (geometric mean, 160 ng/g); hexachlorobenzene ranged from nondetectable levels to 180 ng/g lipid (geometric mean, 17 ng/g); and ∑hexachlorocyclohexane levels ranged from 1.2 to 1,500 ng/g lipid (geometric mean, 16 ng/g). Using nuclear magnetic resonance–based metabonomics, samples (n = 7) containing the highest contaminant levels were compared with samples (n = 7) containing the lowest levels. Excellent separation along the first principal component implied that the chemical constituents of the two groups were significantly different. Although reasons for such differences remain obscure, lifestyle factors associated with a more heterogeneous London cohort could be responsible. Identifying primary routes of contaminant exposures and their biologic effects is of great importance.

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. gamma-Hexachlorocyclohexane (gamma-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 alpha or beta 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.

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