February 18, 2014 | by Hiu Chung So
Humans are exposed to countless chemicals every day, so identifying the ones that can impact their health – specifically the ones that can increase cancer risk – is akin to looking for a sugar crystal in a salt shaker.
But that process has now been made much less arduous by researchers at City of Hope. They've developed a screening test that can analyze 16 times as many chemicals as conventional means. The test — called AroER tri-screen™ — can quickly analyze up to 1,536 compounds' effect on estrogen and aromatase, an enzyme that converts androgen to estrogen.
The results verifying this novel screening method — and discovering that the antidepressant paroxetine (Paxil) acts as an estrogen promoter —are published ahead of print online in Toxicological Sciences.
“Approximately 70 percent of breast cancers are sensitive to estrogen, and exposure to estrogen-disrupting compounds — especially during the critical periods of pregnancy, childhood and adolescence — can have an irreversible impact on still-developing bodies,” said Shiuan Chen, Ph.D., professor and chair of City of Hope’s Department of Cancer Biology and lead author of the study. “Thus, it makes sense to develop this test, which can assess many chemicals at once, to help us quickly identify which environmental compounds are disrupting estrogen functions.”
The screening method uses a microplate, a special plate containing miniature test tubes known as wells. In the wells are specially cultured estrogen-sensitive breast cancer cells treated to detect either estrogen-promoting or estrogen-suppressing properties of chemicals.
After verifying this method in a standard 96-well microplate with known estrogen disrupters, such as bisphenol A, the researchers collaborated with the Tox-21 program (a national effort to develop methods to screen for hazardous chemicals) to amplify the number of wells in the microplate — from 96 to 1,536. That amplification greatly increased the number of assessments each test could process.
In a second round of tests, the researchers not only confirmed AroER tri-screen’s effectiveness on a larger scale, they also found that antifungal medications oxiconazol (Oxistat) and bifonazole (Canespor) exhibited aromatase-inhibiting properties, while the antidepressant paroxetine (Paxil) acted as an estrogen promoter.
“The paroxetine finding helps explain previous studies showing that it reduces tamoxifen therapy’s effectiveness,” Chen said. “And it has implications for patients with estrogen-sensitive breast cancer who are on other medications.”
Given these promising findings, Chen said, he hopes that the AroER tri-screen assay will be be used to assess the estrogen-disrupting properties of more compounds, including medications, environmental pollutants and common household chemicals.
Such compounds also can disrupt the functions of other hormones, Chen said, potentially raising the risk of obesity and diabetes later in life. He hopes that the AroER tri-screen method can be adjusted to screen for the chemicals' effects on other endocrine hormones as well.
The project was supported by the California Breast Cancer Research Program (17UB-8701) with the goal to develop such a screening system to identify environmental chemicals with impact on breast cancer development.
Other researchers involved in this study include Dujin Zhou, Ph.D., Li-Yu Hsin, M.S., Noriko Kanaya, Ph.D., Cynthie Wong, Ph.D., Yate-Ching Yuan, Ph.D., and Richard Yip, Ph.D., from City of Hope and Srilatha Sakamuru, Ph.D., Menghang Xia, Ph.D., Kristine Witt, Ph.D., and Christina Teng, Ph.D., from the National Institutes of Health. Research reported in this publication included work performed in the Bioinformatics Core, High Throughput Screening Core and Integrative Genomics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572.
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