Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome

Juliane Winkler; Pengyuan Liu; Kiet Phong; Johanna H Hinrichs; Nassim Ataii; Katherine Williams; Elin Hadler-Olsen; Susan Samson; Zev J Gartner; Susan Fisher; Zena Werb

doi:10.1073/pnas.2115308119

Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome

Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2115308119. doi: 10.1073/pnas.2115308119. Epub 2022 Mar 9.

Authors

Juliane Winkler^{1

2}, Pengyuan Liu^{3

4}, Kiet Phong⁵, Johanna H Hinrichs^{1

6}, Nassim Ataii¹, Katherine Williams³, Elin Hadler-Olsen^{1

7}, Susan Samson^{1

2}, Zev J Gartner^{5

8

9}, Susan Fisher^{1

3}, Zena Werb¹

Affiliations

¹ Department of Anatomy, University of California, San Francisco, CA 94143.
² Department of Cell and Tissue Biology, University of California, San Francisco, CA 94143.
³ Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143.
⁴ Department of Chemistry, University of Massachusetts, Lowell, MA 01854.
⁵ Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158.
⁶ Institute of Internal Medicine D, Medical Cell Biology, University Hospital Münster, 08154 Münster, Germany.
⁷ Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037 Tromsø, Norway.
⁸ The Center for Cellular Construction, University of California, San Francisco, CA 94158.
⁹ Chan Zuckerberg Biohub Investigator, University of California, San Francisco, CA 94158.

Abstract

SignificanceBisphenol A (BPA), found in many plastic products, has weak estrogenic effects that can be harmful to human health. Thus, structurally related replacements-bisphenol S (BPS) and bisphenol F (BPF)-are coming into wider use with very few data about their biological activities. Here, we compared the effects of BPA, BPS, and BPF on human mammary organoids established from normal breast tissue. BPS disrupted organoid architecture and induced supernumerary branching. At a proteomic level, the bisphenols altered the abundance of common targets and those that were unique to each compound. The latter included proteins linked to tumor-promoting processes. These data highlighted the importance of testing the human health effects of replacements that are structurally related to chemicals of concern.

Keywords: bisphenols; breast cancer; global proteomics; mammary gland; organoids.

MeSH terms

Benzhydryl Compounds* / toxicity
Carcinogenesis* / chemically induced
Estrogens* / toxicity
Humans
Mammary Glands, Human* / drug effects
Mammary Glands, Human* / pathology
Organoids / drug effects
Organoids / pathology
Phenols* / toxicity
Proteome* / drug effects
Proteomics
Sulfones* / toxicity

Substances

Benzhydryl Compounds
Estrogens
Phenols
Proteome
Sulfones
bisphenol F
bis(4-hydroxyphenyl)sulfone
bisphenol A