Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent

Abstract

Benzophenone-3 is a putative endocrine disrupting chemical and common ingredient in sunscreens. The potential of endocrine disrupting chemicals to act as agonists or antagonists in critical hormonally regulated processes, such as mammary gland development and mammary tumorigenesis, demands evaluation of its potential in promoting breast cancer. This study identifies the effects of BP-3 on mammary tumorigenesis with high-fat diet during puberty versus adulthood in Trp53-null transplant BALB/c mice. Benzophenone-3 exposure yielded levels in urine similar to humans subjected to heavy topical sunscreen exposure. Benzophenone-3 was protective for epithelial tumorigenesis in mice fed lifelong low-fat diet, while promotional for epithelial tumorigenesis in mice fed adult high-fat diet. Benzophenone-3 increased tumor cell proliferation, decreased tumor cell apoptosis, and increased tumor vascularity dependent on specific dietary regimen and tumor histopathology. Even in instances of an ostensibly protective effect, other parameters suggest greater risk. Although benzophenone-3 seemed protective on low-fat diet, spindle cell tumors arising in these mice showed increased proliferation and decreased apoptosis. This points to a need for further studies of benzophenone-3 in both animal models and humans as a potential breast cancer risk factor, as well as a more general need to evaluate endocrine disrupting chemicals in varying dietary contexts.

44-Year Retrospective Analysis of Ultraviolet Absorbents and Industrial Antioxidants in Seabird Eggs from the Canadian Arctic (1975 to 2019)

“…In addition, it is recognized as an endocrine disruptor that can produce a number of reproductive adverse effects in humans, including sex-dependent alterations in birth weight and gestational age, as well as decreased epididymal sperm density in male rats and a longer estrous cycle in female rats . Furthermore, BP3 has been linked to mammary gland cancer …”

Exposure to Low Doses of Oxybenzone During Perinatal Development Alters Mammary Gland Stroma in Female Mice

“…Depending on the region, season, and individual use of oxybenzone-based personal care product, both doses are likely relevant to human exposures based on back-calculations of urinary concentrations NHANES studies ( Woodruff et al, 2011 ; Han et al, 2016 ). Furthermore, considering differences in the toxicokinetics between species, both exposures are likely below human exposure levels experienced during sunscreen application ( Kariagina et al, 2020 ; Matouskova and Vandenberg, 2022b ). Although the dermal route of exposure results in systemic exposure in humans and rodents, the more controlled approach using an oral route of exposure leads to systemic concentrations of oxybenzone similar to dermal application in mice ( Matta et al, 2020 ; Mutlu et al, 2020 ).…”

“…A second study found that mice exposed to oxybenzone during perinatal development had increased numbers of epithelial structures in adulthood, including the precocious appearance of alveolar buds, differentiated structures which are typically associated with pregnancy ( Matouskova et al, 2020 ). Finally, a third study using a genetically susceptible mouse model found that oxybenzone promoted epithelial tumors in the mammary gland when mice were fed a high-fat diet throughout adulthood ( Kariagina et al, 2020 ).…”

Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?

“…Moreover, acute exposures to environmentally relevant concentrations of benzophenone-3 induced genotoxicity and mutagenesis in Poecilia reticulata by inducing DNA damages and nuclear abnormalities in the erythrocytes (Almeida et al, 2019). There is no information about the benzophenone-3 on promotion/progression of the skin cancer, but lately benzophenone-3 has been found to promote mammary tumorigenesis and to increase metastasis in lung cancer cells via epithelial to mesenchymal transition (Phiboonchaiyanan et al, 2017;Kariagina et al, 2020).…”

“…Moreover, benzophenone-3 causes long-term changes in the morphology and function of the mammary gland and delays breast development by 5-6 months in young women (Wolff et al, 2015;LaPlante et al, 2018). Additionally, benzophenone-3 has been identified as a potential breast cancer risk factor since it increases tumor cell proliferation and vascularity and decreases tumor cell apoptosis (Kariagina et al, 2020). According to recent data, benzophenone-3 is associated with a higher risk of endometriosis in women (Peinado et al, 2021).…”