Considering BPA: State of the Art or Willful Ignorance? June 13, 2012 CPMC, Physician Resource, San Francisco Medicine, SFMS Member bisphenol A, Shanaz Dairkee, William Goodson III, BPA 0 By William H. Goodson III, MD, and Shanaz H. Dairkee, PhD “The Food and Drug Administration said Friday that it lacks scientific information to ban the chemical bisphenol A from food containers.” —Wall Street Journal, March 31, 2012 “ ...FDA supports reasonable steps to reduce exposure of infants to BPA in the food supply… FDA will support changes in food can linings and manufacturing to replace BPA to minimize BPA levels….” —U.S. Food and Drug Administration website, March 30, 2012. While it is technically correct that the FDA did not ban bisphenol A (BPA), the Wall Street Journal misled readers when it ignored the clear FDA statements that we need to reduce BPA exposure of our most vulnerable citizens. This is a prototype example of the spin-versus-spin arguments that characterize most of the environmental chemical debate. These arguments are not about truth. They are about control of public perception. It is time for willful efforts to skip the spin, outline the challenges, and answer the questions that affect the safety of our children and grandchildren. The BPA debate centers around three types of data: BPA promotes breast cancer in animals. Animals exposed to BPA, either in utero or through nursing from dams fed BPA, develop breast epithelial abnormalities and are more susceptible to breast cancer induction by the carcinogen dimethylbenzanthracene (DMBA). Like natural estrogen, BPA stimulates growth of human breast cancer cells transplanted into mice. This is not unexpected, because BPA has been known since the 1930s to act as an estrogen. Note: The concern is not that BPA by itself causes cancer but rather that, through excessive estrogenic stimulation, it promotes cancer. The debate centers on the relation of animal doses to human exposure. In cell culture studies, BPA causes nonmalignant human breast epithelial cells (obtained by fine needle aspiration from women volunteers) to grow faster and evade apoptosis (programmed cell death), a necessary step for radiation and drugs to kill tumor cells. These changes are referred to as hallmarks of cancer because they are prerequisites for cancer to occur. BPA by itself is sufficient to induce these abnormalities. It is especially relevant that they occur in nonmalignant cells, because these are the target cells that must undergo the required changes for breast cancer to occur. These changes occur in concentrations that are found in fetuses, mothers, and mother’s milk. Although most of us ingest BPA daily, it is metabolized quickly. Recent studies have shown that BPA in canned soups and similar products causes a spike in serum BPA, followed by a rapid fall back to preingestion levels. Some critics conclude from this that BPA cannot be around long enough to cause harm. The real situation, however, is more complicated. First, clearance may not be functionally permanent. Most clearance is by conjugation to glucuronate, a frequent mechanism to clear hormones, chemicals, and drugs from the blood. However, the enzyme glucuronidase can deconjugate BPA from glucuronate, and significant levels of glucuronidase are present in many tissues. In the case of the breast, biologically active glucuronidase is present in mother’s milk and, for example, contributes to neonatal jaundice by deconjugating the baby’s bilirubin in the gut. It is difficult to expect that the BPA known to be in human breast milk would not be activated the same way. Second, it is argued that BPA rises and falls too quickly to cause harm, but this ignores what reproductive endocrinologists have known for years. Reproduction responds to spikes in hormone levels as much or more as to constantly elevated hormone levels. It may be that spikes, such as from a preadolescent eating BPA-rich food, would pose a greater risk. These studies do not imply that BPA by itself causes breast cancer, but rather the estrogenic activity of BPA causes changes that promote breast cancer. The cancer-promoting properties of estrogens are the reason millions of women discontinued menopausal hormone replacement therapy after the Women’s Health Initiative showed that combination estrogen plus progestin therapy increased breast cancer. Unfortunately, women living in the United States cannot decide to discontinue their exposure to BPA. BPA is present in food packaging, house dust, cash register receipts, etc., such that 95 percent of Americans and 90 percent of Canadians test positive for BPA in their urine. Thirty years ago, Lippman and Bolan recognized the importance of cell culture “ . . . in the analysis of estrogen action in nonmalignant tissue . . . ” In our work with nonmalignant cells, we have identified six different major cell features that are altered by BPA in ways that promote hallmark, cancer-like behavior in previously benign cells. The irony in this battle of spin is that if we had a drug that turned off cancer cells in culture as much as BPA turns them on, if we had data showing a clear mechanism of action like we have for BPA, and if we had as much supportive animal exposure data as already exists for BPA, the hypothetical drug would be expeditiously lined up for clinical trials. It is time for responsible parents and grandparents to demand an end to the battle of spin. Calm minds must sort through the facts objectively and design and perform the studies needed to resolve pertinent questions. William H. Goodson III, MD, is a breast cancer specialist, senior clinical research scientist at CPMC Research Institute, and former a SFMS president. Shanaz H. Dairkee, PhD, is senior scientist, CPMC Research Institute. References Carwile JL, Ye X, Xiaoliu Z, Calafat AM, Michels KB. Canned soup consumption and urinary bisphenol A: A randomized crossover trial. JAMA. 2011; 306(20):2218-2220. Dairkee SH, Seok J, Champion S, Sayeed A, Mindrinos M, Xiao W, Davis RW, Goodson WH. Bisphenol A induces a profile of tumor aggressiveness in high-risk cells from breast cancer patients. Cancer Res. 2008; 68(7):2076-80. Goodson WH III, Luciani MG, Sayeed SA, Jaffee IM, Moore DH II, Dairkee SH. Activation of the mTOR pathway by low levels of xenoestrogens in breast epithelial cells from high-risk women. Carcinogenesis. 2011; 32(11):1724-33. Teeguarden JG, Calafat AM, Ye X, Doerge DR, Churchwell MI, Gunawan R, Graham MK. Twenty-four hour human urine and serum profiles of bisphenol a during high-dietary exposure. Toxicol Sci. 2011; 123(1):48-57. Comments are closed.
