Journal article
Estrogenicity and androgenicity screening of PCB sulfate monoesters in human breast cancer MCF-7 cells
Environmental science and pollution research international, Vol.23(3), pp.2186-2200
02/2016
DOI: 10.1007/s11356-015-5142-y
PMCID: PMC4718780
PMID: 26300354
Abstract
Recent studies identified polychlorinated biphenyl (PCB) sulfate esters as a major product of PCB metabolism. Since hydroxy-PCBs (HO-PCBs), the immediate precursors of PCB sulfates and important contributors to PCB toxicity, were shown to have estrogenic activity, we investigated the estrogenicity/androgenicty of a series of PCB sulfate metabolites. We synthesized the five possible structural sulfate monoester metabolites of PCB 3, a congener shown to be biotransformed to sulfates, a sulfate ester of the paint-specific congener PCB 11, and sulfate monoesters of two HO-PCBs reported to interact with sulfotransferases (PCB 39, no ortho chlorines, and PCB 53, 3 ortho chlorines). We tested these PCB sulfates and 4'-HO-PCB 3 as positive control for estrogenic, androgenic, anti-estrogenic, and anti-androgenic activity in the E- and A-screen with human breast cancer MCF7-derived cells at 100 μM-1 pM concentrations. Only 4'-HO-PCB 3 was highly cytotoxic at 100 μM. We observed structure-activity relationships: compounds with a sulfate group in the chlorine-containing ring of PCB 3 (2PCB 3 and 3PCB 3 sulfate) showed no interaction with the estrogen (ER) and androgen (AR) receptor. The 4'-HO-PCB 3 and its sulfate ester had the highest estrogenic effect, but at 100-fold different concentrations, i.e., 1 and 100 μM, respectively. Four of the PCB sulfates were estrogenic (2'PCB 3, 4'PCB 3, 4'PCB 39, and 4'PCB 53 sulfates; at 100 μM). These sulfates and 3'PCB 3 sulfate also exhibited anti-estrogenic activity, but at nM and pM concentrations. The 4'PCB 3 sulfate (para-para' substituted) had the strongest androgenic activity, followed by 3'PCB 3, 4'PCB 53, 4PCB11, and 4PCB 39 sulfates and the 4'HO-PCB 3. In contrast, anti-androgenicity was only observed with the two compounds that have the sulfate group in ortho- or meta- position in the second ring (2'PCB 3 and 3'PCB 3 sulfate). No dose-response was observed in any screen, but, with exception of estrogenic activity (only seen at 100 μM), endocrine activity was often displayed at several concentrations and even at 1 pM concentration. These data suggest that sulfation of HO-PCBs is indeed reducing their cytotoxicity and estrogenicity, but may produce other endocrine disruptive activities at very low concentrations.
Details
- Title: Subtitle
- Estrogenicity and androgenicity screening of PCB sulfate monoesters in human breast cancer MCF-7 cells
- Creators
- Susanne Flor - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, 100 Oakdale Campus, 214 IREH, Iowa City, IA, 52242-5000, USAXianran He - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, 100 Oakdale Campus, 214 IREH, Iowa City, IA, 52242-5000, USAHans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, 100 Oakdale Campus, 214 IREH, Iowa City, IA, 52242-5000, USAGabriele Ludewig - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, 100 Oakdale Campus, 214 IREH, Iowa City, IA, 52242-5000, USA. gabriele-ludewig@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Environmental science and pollution research international, Vol.23(3), pp.2186-2200
- DOI
- 10.1007/s11356-015-5142-y
- PMID
- 26300354
- PMCID
- PMC4718780
- NLM abbreviation
- Environ Sci Pollut Res Int
- ISSN
- 0944-1344
- eISSN
- 1614-7499
- Publisher
- Germany
- Grant note
- P30 ES005605 / NIEHS NIH HHS P30 ES05605 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS P30 CA030199 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 02/2016
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Radiation Oncology; Iowa Superfund Research Program
- Record Identifier
- 9983997301902771
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