Giovanna Di Sauro

In these days you might have heard some reporting about Health Canada officially stating that they consider bisphenol A to be a chemical potentially dangerous for human health, and that plastic bottles containing bisphenol A-based lining are starting to get pulled out (voluntarily) of stores. This announcement is coming out at the same time as two papers, published in the journal Cancer Research. One documents that bisphenol A (also known as BPA) induces changes in gene expression in breast cancer cell lines coherent with those of high-grade lesions; the other shows that BPA is also able to alter the epigenetic profile in the progeny of BPA-treated epithelial cells.

But it would be a mistake to base a discussion on BPA only referring to these two papers and recent events; in fact, the academic discussion regarding BPA effects on our environment, ecology, and health has been ongoing – since the 1960s. And potential carcinogenicity is only the tip of the iceberg: a PubMed search using the terms “bisphenol A AND estrogen” generated 1375 hits, while a similar search, using the terms “bisphenol A AND estrogen AND cancer”, only generated 165 hits.

I am therefore going to split this article into two parts. In this first part, I will introduce the concept of xenoestrogens, talk a little bit about what bisphenol A is and what is used for, and tell the story of the discovery of its – initially unsuspected – effects on systems usually regulated by estrogen and similar hormones. In the second part, I will talk about the research regarding BPA potential toxicity, carcinogenicity, and the medical and ecological implications of BPA presence in our environment.

First of all, let’s get to know the steroid hormones, a hormone family estrogens are happy members of. That’s right – estrogens: this is a sub-family of steroid hormones. There are three main estrogens in humans: estradiol, estriol, and estrone, produced from androgens. The process of producing steroid hormones (both male and female) from cholesterol is called steroidogenesis. Here is a sketch of the process (click on the thumbnail to get to the full-sized image).

Estrogens are important for the determination of female secondary sexual characters, and not only in humans. They function during development, and during certain types of tumorigenesis. On the other side of the family, we find the androgens, the male-determining hormones. They are also derived from cholesterol…and in fact, estrogens are produced after chemical modification of some androgens. A commonly known androgen is testosterone.

Some man-made (say, BPA) or natural (for instance phytoestrogen) compounds with a structure close to that of the steroid hormones are able to sometimes reproduce the physiological effects of these hormones. These are sometimes called xenoestrogens – literally, foreign estrogens. How was it discovered that BPA is in fact a xenoestrogen?

One of the studies documenting this discovery was a perfect example of serendipity. Researchers at Stanford University were trying to find out whether the yeast Saccharomyces cerevisiae is able to produce estrogen. To do this, they decided to grow the yeast in common flasks, and to run an assay for endogenously produced estrogen. They quickly realized that radioactively-labelled estradiol added to the growth medium was being displaced by estrogen coming from another source. This source turned out to be not the yeast, but the polycarbonate flasks themselves. The substance causing the effect was purified using high-performance liquid chromatography (HPLC), and was found to be BPA. Tests on mammalian cells showed that BPA was effectively an estrogenic compound, able to induce expression of progesterone receptors, and to bind estrogen receptors in mammalian cells.

We now know that BPA’s ability to mimic endogenous estrogen has the ability to affect the reproductive system, and sexual development – at least in frogs. The sex ratio in frogs being exposed to BPA is altered, and feminization can be observed when frogs are exposed, as tadpoles, to varying concentrations of BPA – and this correlates with an increased expression of the estrogen receptor.

What is BPA, and why is it used? Bisphenol A is a compound that can be used to create polymeric plastics. Most specifically, BPA finds its main use in the production of polycarbonate plastics, which are hard to shatter, and therefore used, among other things, in laboratory glassware, bottles for drinking water and food containers. Polycarbonates are also used as sealers – found in the lining of plastic bottles or tin cans. Polycarbonate plastics are extremely resistant to heat and mechanical stress, but bleach and strong alkali can cause the release of BPA from the plastic. And apparently, these plastics initially leak low levels of BPA when exposed to boiling water, about 55 times more than when the water is at room temperature.

But is this leakage dangerous for human and animal health? Is the evidence in favor (or against) its health effects reliable, unbiased and coherent? Is it safe to use polycarbonate containers for your water and food? We will find out more about this in the next post.

Post Scriptum: this post was kindly included in the latest edition of Tangled Bank.

Citations

Krishnan, A.V. (1993). Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving.. Endocrinology, 132(6), 2279-2286.

Levy
, G. (2004). Bisphenol A induces feminization in Xenopus laevis tadpoles. Environmental Research, 94(1), 102-111. DOI: 10.1016/S0013-9351(03)00086-0

LE, H., CARLSON, E., CHUA, J., BELCHER, S. (2007). Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons. Toxicology Letters DOI: 10.1016/j.toxlet.2007.11.001

Maragou, N., Makri, A., Lampi, E., Thomaidis, N., Koupparis, M. (2008). Migration of bisphenol A from polycarbonate baby bottles under real use conditions. Food Additives & Contaminants, 25(3), 373-383. DOI: 10.1080/02652030701509998

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