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Proteomic effects of potential endocrine-disrupting compounds
herbicide in the U.S. and other nonEU countries, however. David Carpenter of the University at Albany, State University of New York, applauds the inclusion of atrazine in the current study because its effects on the endocrine system have not been well characterized. PCBs, which are industrial pollutants, are usually found in the envi-
Endocrine-disrupting compounds (EDCs) interfere with hormonal signaling. Those that mimic or block sex hormones have received the most attention, but EDCs also can affect thyroid function, insulin signaling, and bone growth. To better understand the effects of EDCs in human cells, Torsten Bohn, Arno Gutleb, and colleagues at the Centre de Recherche Public Gabriel Lippmann and the National Public Health Laboratory (both in Luxembourg) conducted a proteomic study. In JPR (2009, DOI 10.1021/pr900480f), they report that atrazine and polychlorinated biphenyl (PCB) 153, two chemicals that are often referred to as EDCs, have wideMany effects. In general, atrazine treatment decreased (and PCB ranging effects on the proincreased) the levels of many proteins compared with controls. teomes of breast-cancer cells. The classification of ronment as mixtures of congeners, or some chemicals as EDCs is still up structural variants. The researchers for debate, says Bohn. Some reports chose to study PCB 153 because it is show endocrine-disrupting effects in one of the most common congeners animals such as amphibians, but it and is typically observed in high concan be difficult to extrapolate the recentrations. A worldwide ban on sults of these studies to humans. PCBs took effect in the late 1970s, Many EDCs are present in the envibut these compounds are still freronment in mixtures. “There might quently detected. PCB 153 “is almost be additive or synergistic effects,” he not metabolized, which means it is explains, so it can be difficult to dequite stable in the environment,” termine the effects of individual Gutleb points out. The study of only chemicals. “We think there is a cerone congener could be considered a tain likelihood that [atrazine and PCB limitation of the study, notes Virginie 153] can indeed perturb human Gillardin of the University of Namur physiological processes and act as (Belgium). However, Bohn says that endocrine disruptors, but you cannot the team may study the effects of say it is really proven,” he states. mixtures in the future. Not only do EDCs wreak havoc on To get a handle on the proteomic human physiology, but some of these effects of atrazine and PCB 153, the compounds are also highly stable in researchers treated MCF-7 human the environment. Although the use of breast-cancer cells with the chemicals. atrazine, an herbicide, is forbidden in MCF-7 cells are models for endocrine the European Union (EU), the chemidisruption because they are sensitive cal can be detected there. “We did to estrogen. A positive control of 17-β measurements here in Luxembourg estradiol and a negative control of soland still found significant concentravent alone were also included. Proteins tions in the groundwater, despite its were analyzed by 2D difference gel banishment a couple of years ago,” electrophoresis (known as DIGE). Bohn says. Atrazine is still a popular
10.1021/pr900934m
© 2009 American Chemical Society
A total of 22 proteins were differentially expressed in the atrazine- or PCB-treated cells compared with controls. Some proteins responded specifically to only one of the treatments, whereas other proteins were differentially expressed in response to both chemicals. The identified proteins are involved in a wide range of processes, including transcription, stress regulation, and cell structure. In addition, the proteins are located in various cellular compartments. “What we generally found was that atrazine led to underexpression, and PCB led to overexpression of proteins,” says Bohn. Gillardin says that proteomic studies, such as this one, on potential EDCs are sorely needed. treatment “There are numerous studies that use transcriptomics to assess the impact of PCBs on different organisms or cell lines,” she states. “However, the data concerning the effects of PCBs on protein expression remain scarce.” Carpenter notes, “I think it’s an excellent paper. It’s exactly the direction we should be going [in] to understand the mechanism of endocrine disruption.” Currently, the researchers are conducting transcriptomic experiments, as well as verifying the proteins they identified in the paper. “The first study was really to have an indication of which proteins could be involved and which proteins we would likely follow and focus on in the future,” says Bohn. Carpenter points out that figuring out exactly how these proteins function in response to chemical treatment would be an important future direction. He also suggests human studies be performed. Gillardin proposes that the group analyze additional cell lines. Bohn notes that the researchers may, in fact, analyze other cell lines, as well as various exposure times and concentrations. —Katie Cottingham
Journal of Proteome Research • Vol. 8, No. 12, 2009 5411
