A new study has reported a mechanism by which prenatal exposure to bisphenol-A (BPA) or diethylstilbestrol (DES) increases the risk of mammary tumors in mice. BPA and DES are estrogen-like chemicals that induce persistent changes influencing the expression of the genes in the developing uterus. BPA is used in the lining of metal food and beverage cans and is also found in polycarbonate bottles (identified by the recycling number 7 embossed in the base of the bottles). Fetal DES exposure is known to be associated with increased risk of subsequent breast cancer in adulthood. Similarly, fetal exposure to BPA has been found to induce cancerous changes in mouse mammary tissue.
In the study, the effect of BPA and DES on EZH2 expression and function in MCF-7 human breast cancer cells and in mammary glands of mice exposed in utero were investigated. Overexpression of EZH2 (enhancer of zeste homolog 2) has been linked to breast cancer risk and regulation of cancer development. Mice were treated with BPA and DES approximating human exposure and EZH2 functional activity was measured. Treatment of hormone receptor positive MCF-7 cells with BPA or DES resulted in two- and three-fold increases in EZH2 mRNA expression, respectively. EZH2 was elevated in adult mammary tissue of mice exposed to BPA or DES. Elevated EZH2 levels are associated with increased risk of breast cancer in humans.
The authors conclude that developmental programming of EZH2 is a mechanism by which in utero exposure to endocrine disruptors leads to epigenetic regulation of the mammary gland. Epigenetic changes are modifications in gene expression caused by heritable, but potentially reversible, changes such as changes in DNA methylation and microRNAs. Epigenetic changes are easily influenced by dietary and environmental factors. In a separate interview, the lead author of the study, Hugh Taylor, MD, of the Yale University School of Medicine, commented that "this study generates important safety concerns about exposures to environmental endocrine disruptors such as BPA and suggests a potential need to monitor women exposed to these chemicals for the development of breast lesions as adults."
BPA and other endocrine disruptors are found in some plastics
Some plastics contain estrogenic and otherwise carcinogenic chemicals that can leach into food when the plastics are heated, microwaved, put under pressure or simply scuffed and worn. These chemicals include BPA, styrene, and phthalates. Plastics that may leach these substances include (1) polyvinyl chloride (PVC), which may be found in cling wrap, some plastic squeeze bottles, and cooking oil bottles; (2) polystyrene, which may be found in styrofoam food containers and disposable cups and bowls; and (3) polycarbonates, which may be found in soup and soda can linings, plastic baby bottles, water bottles, and clear plastic sippy cups. Children and adults alike should avoid all but temporary, low temperature uses of these products. Plastic containers may be marked with a number in a triangle-like icon. Plastics marked 1, 2, 4 or 5 use less toxic additives in their manufacture. Products that use polyvinyl chloride should be marked with 3, polystyrene with a 6, and polycarbonate with a 7 — these are the ones to avoid.