Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide. It can be detected in the body fluids of more than 90% of the human population. Originally deliberately created as an estrogenic compound, it is now used as an industrial plasticizer in a wide variety of applications. For example, it is used in the manufacture of food and beverage containers and it leaches from these containers during normal usage. BPA has been found to promote mammary tumor development at environmentally relevant doses in mouse models of breast cancer. Perinatal exposure to BPA has also been shown to increase mammary tumors in mouse offspring. Now a new study has demonstrated that BPA promotes tumor development in mice by mimicking the actions of estradiol (E2) in binding to estrogen receptor alpha (ERα).
Sources of BPA exposure
Bisphenol A is used to manufacture polycarbonate plastics found in plastic baby bottles, water bottles, and plastic containers. BPA is also found in various canned goods, where it leaches from the epoxy coatings used to prevent corrosion of can interiors. In addition to food cans, soda cans are often lined with plastic that contains bisphenol A. BPA is pervasive in household dust. Consumer protections with respect to bisphenol A are weak. Bisphenol-S (BPS) is now starting to be used as a bisphenol-A substitute and has been described as safer than BPA. However, recent research suggests BPS has harmful effects similar to that of BPA.
Latest research shows BPA produces carcinogenic effects by binding to ERα
The study referenced at the beginning of this news story was designed to investigate the carcinogenic potential of BPA. Activation of ERα by estradiol can trigger a series of downstream signaling pathways involved in both normal and abnormal physiology of the human reproductive system. Note that there are two types of estrogen receptors: ERα and estrogen receptor beta (ERβ). Some compounds that bind to ERα do not bind to ERβ and vice versa. Both types of estrogen receptor are therapeutic targets in breast cancer. Estradiol is produced naturally in the body. However, some other compounds (including some that are dissimilar to estradiol) also bind to ER. The resulting unintentional activation of ER signaling in reproductive tissues can result in cancer development. BPA is an estrogen-like chemical that has been shown to activate ERα in cell studies.
To conduct the study, the authors first developed a unique transgenic mouse model to investigate the dynamics and potency of chemicals that bind to ERα. A specialized ERα folding biosensor was incorporated. This model was validated using a variety of such compounds, including Diethylstilbestrol (DES), Raloxifene, Tamoxifen and estradiol itself. The authors then investigated the carcinogenic property of BPA in the mice by subjecting them to long-term exposure at full or half environmental doses. Activation of downstream ERα signaling was confirmed using bioluminescence imaging. BPA induced tumor-like outgrowths in the mice, which were histopathologically confirmed to be cancerous and epithelial in origin. The authors conclude that exposure to BPA has significant carcinogenic effects on female mice through activation of ERα.
Please see our article on BPA and breast cancer for more information.