In the United States, 1 in 8 women will develop breast cancer, according to the American Cancer Society, and many of them are unwittingly making a serious choice every time they apply sunscreen: should they expose their skin to the sun or their mammary cells to a potentially cancer-causing chemical?
MSU Professor Richard Schwartz led a landmark study showing the common sunscreen ingredient Benzophenone-3, also known as oxybenzone or BP-3, combined with diet, plays a role in the development of mammary gland tumors. Credit: G.L. Kohuth
Research led by Michigan State University researchers in the College of Natural Science is the first of its kind to show that the common sunscreen ingredient benzophenone-3, also known as oxybenzone or BP-3, can play a role in the development of mammary gland tumors.
The five-year study, funded by the Breast Cancer and the Environment Research Program housed in the National Institute for Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI), was recently published in Oncotarget.
“Our set of results suggest caution in using BP-3 and the need to dig deeper to understand what it can do in mammary glands and tumorigenesis,” said Richard Schwartz, professor in the Department of Microbiology and Molecular Genetics, who has been researching the interaction of diet and cancer cell growth and proliferation for more than 12 years.“This is the first published result that makes a convincing case that BP-3 can change cancer outcomes.”
Schwartz and co-author Sandra Haslam, professor emeritus in the Department of Physiology, previously conducted successful experiments in mouse models that elucidated a relationship between diets high in saturated animal fats with higher incidence and shorter latency of breast cancer.
“We were excited about the results of our diet experiments, but the NIEHS was interested in funding a chemical study, so we decided to combine the two,” Schwartz said.
The leftward shift of tumors from mice treated with oxybenzone (BP-3) while fed a high-fat diet during adulthood (LFD-HFD) shows the increased number and rapid appearance of mammary gland tumors. Credit: Schwartz Lab
The researchers landed on BP-3, a ubiquitous and easily absorbed chemical. A recent report in the Journal of the American Medical Association found that after just one heavy application of sunscreen, blood levels of BP-3 exceeded the Federal Drug Administration’s guidance for chemicals at a threshold of toxicological concern, and the Centers for Disease Control found BP-3 in 98 percent of adult urine samples.
BP-3 is also a suspected endocrine disrupting chemical (EDC), substances that interfere with hormonally regulated processes the body uses for a wide range of functions, including mammary gland development.
Using a mouse model where the mammary glands lacked a gene often mutated in human breast cancer as a proxy for women growing from puberty into adulthood, the scientists put the mice under three distinct dietary regimes: a lifelong low-fat diet, a high-fat diet during puberty switching to a low-fat diet during reproductive years and vice versa.
The experiment split mice on these three diets into two groups. One of these groups was fed BP-3 daily at a dose equivalent to a heavy application of sunscreen on a beach day.
Over the course of a year and a half of treatment, the researchers collected tumors from the mice and found robust evidence for the adverse effects of diet and BP-3 on breast cancer development.
“You never know what you’re going to find in experiments like these,” Schwartz said. “I was prepared to see no difference at all from BP-3 in any of our diets, but we found that even a relatively brief exposure to a high-fat diet during puberty is enough to allow BP-3 to cause a change in the outcome for cancer.”
Nearly all mice developed two kinds of aggressive breast cancer tumors. The first, known as epithelial tumors, retain many of the properties of normal mammary gland cells. The second,
A fluorescent image of apoptotic cells (green) undergoing programmed cell death within a mammary gland tumor. Oxybenzone can cause less programmed cell death in spindle cell tumors that occur in animals fed a low-fat diet, a correlate of more aggressive tumors. Credit: Schwartz Lab
known as spindle cell tumors, lose most of the properties of normal cells and develop into a deadly, often triple negative form of breast cancer known as claudin-low breast cancer.
The effects of BP-3 varied depending on when the mice were fed a certain type of diet. For example, mice given a lifelong low-fat diet surprisingly acquired some protection against epithelial tumors from the chemical BP-3 but had spindle cell tumors with more aggressive properties. A high-fat diet during puberty, on the other hand, completely blocked any protective effect of BP-3 and caused epithelial tumors to grow more aggressively. The last treatment, a high-fat diet during adulthood, promoted aggressive epithelial tumors.
Interestingly, the researchers also found that before tumors appeared, BP-3 increased the growth of normal breast cells on all diets, a known correlate of more aggressive cancers.
“BP-3 will likely not have the same impact on groups of women with dietary differences, and that’s an important question to ask when designing experiments that study the effects of EDC’s and cancer,” Schwartz explained. “In balance, these results suggest that there are enough bad effects from BP-3 overall that we believe it calls for the precautionary principle.
“When there are alternatives, stay away from BP-3,” recommended Schwartz, who noted that zinc oxide and titanium dioxide creams are good candidates.
The grant supporting Schwartz’s bench research also encompassed areas of epidemiology and outreach. Epidemiologists at the University of Cincinnati are studying a cohort of young women at varying ages and levels of BP-3 to track any reproduction abnormalities. A breast cancer advocacy group, the Huntington Breast Cancer Action Coalition, is generating messages for women in New York with help from the grant, and Schwartz collaborated with health science communication researchers at MSU.
To read the landmark paper, released at the beginning of December, visit: https://www.oncotarget.com/article/27831/.
Story via MSU College of Natural Science