Total Effective Xenoestrogen Burden in Serum Samples and Risk for Breast Cancer in a Population-Based Multicase–Control Study in Spain

Pastor-Barriuso, Roberto; Fernández, Mariana F.; Castaño‐Vinyals, Gemma; Whelan, Denis R.; Pérez‐Gómez, Beatriz; Llorca, Javier; Villanueva, Cristina M.; Guevara, Marcela; Molina-Molina, José-Manuel; Artacho‐Cordón, Francisco; Barriuso-Lapresa, Laura; Tusquets, Ignasi; Dierssen-Sotos, Trinidad; Aragonés, Núria; Olea, Nicolás; Kogevinas, Manolis; Pollán, Marina

doi:10.1289/ehp157

Cited by 49 publications

(40 citation statements)

References 34 publications

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“…Exposure of xenoestrogens was implicated in breast cancer risk (Pastor-Barriuso et al 2016) as well as resistance to breast cancer treatment (Goodson et al 2011;Warth et al 2018) due to their endocrine actions. The median urinary level of BP-3 was 0:137 lM, and PP was 0:161 lM in nonpregnant women in participating in the NHANES by the CDC (Calafat et al 2010;Woodruff et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Effects of Benzophenone-3 and Propylparaben on Estrogen Receptor–Dependent R-Loops and DNA Damage in Breast Epithelial Cells and Mice

Majhi

Sharma

Roberts

et al. 2020

Environ Health Perspect

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BACKGROUND: Endocrine-disrupting chemicals have been shown to have broad effects on development, but their mutagenic actions that can lead to cancer have been less clearly demonstrated. Physiological levels of estrogen have been shown to stimulate DNA damage in breast epithelial cells through mechanisms mediated by estrogen-receptor alpha (ERa). Benzophenone-3 (BP-3) and propylparaben (PP) are xenoestrogens found in the urine of >96% of U.S. population. OBJECTIVES: We investigated the effect of BP-3 and PP on estrogen receptor-dependent transactivation and DNA damage at concentrations relevant to exposures in humans. METHODS: In human breast epithelial cells, DNA damage following treatment with 17b-estradiol (E 2), BP-3, and PP was determined by immunostaining with antibodies against c-H2AX and 53BP1. Estrogenic responses were determined using luciferase reporter assays and gene expression. Formation of R-loops was determined with DNA: RNA hybrid-specific S9.6 antibody. Short-term exposure to the chemicals was also studied in ovariectomized mice. Immunostaining of mouse mammary epithelium was performed to quantify R-loops and DNA damage in vivo. RESULTS: Concentrations of 1 lM and 5 lM BP-3 or PP increased DNA damage similar to that of E 2 treatment in a ERa-dependent manner. However, BP-3 and PP had limited transactivation of target genes at 1 lM and 5 lM concentrations. BP-3 and PP exposure caused R-loop formation in a normal human breast epithelial cell line when ERa was introduced. R-loops and DNA damage were also detected in mammary epithelial cells of mice treated with BP-3 and PP. CONCLUSIONS: Acute exposure to xenoestrogens (PP and BP-3) in mice induce DNA damage mediated by formation of ERa-dependent R-loops at concentrations 10-fold lower than those required for transactivation. Exposure to these xenoestrogens may cause deleterious estrogenic responses, such as DNA damage, in susceptible individuals.

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Section: Discussionmentioning

confidence: 99%

Effects of Benzophenone-3 and Propylparaben on Estrogen Receptor–Dependent R-Loops and DNA Damage in Breast Epithelial Cells and Mice

Majhi

Sharma

Roberts

et al. 2020

Environ Health Perspect

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“…For instance, an increased breast cancer risk in leaner women was related to the oestrogenicity detected in adipose tissue 16. More recently, serum oestrogenicity was strongly associated with breast cancer risk in a case-control study 17. Along the same line, the antiandrogenic activity of placenta extracts was associated with the risk of urogenital malformations 18.…”

Section: Approaching the Unknownmentioning

confidence: 96%

Know thy unknowns: why we need to widen our view on endocrine disruptors

Wagner

2016

J Epidemiol Community Health

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“…Epidemiological studies add to evidence that EDCs influence the risk of breast cancer [8,9,[37][38][39][40][41], prostate cancer and testicular cancer [37,42,43]. The mechanics of this effect are not yet completely clear and will require further research.…”

Section: Endocrine Disruptors and Human Healthmentioning

confidence: 99%

Endocrine Disruption by Mixtures in Topical Consumer Products

Ripamonti¹,

Allifranchini²,

Todeschi³

et al. 2018

Cosmetics

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Endocrine disruption has been gathering increasing attention in the past 25 years as a possible new threat for health and safety. Exposure to endocrine disruptor has been progressively linked with a growing number of increasing disease in the human population. The mechanics through which endocrine disruptors act are not yet completely clear, however a number of pathways have been identified. A key concern is the cumulative and synergic effects that endocrine disruptors could have when mixed in consumer products. We reviewed the available literature to identify known or potential endocrine disruptors, as well as endocrine active substances that could contribute to cumulative effects, in topical consumer products. The number of endocrine actives used daily in consumer products is staggering and even though most if not all are used in concentrations that are considered to be safe, we believe that the possibility of combined effects in mixtures and non-monotonic dose/response is enough to require further precautions. A combined in vitro approach based on existing, validated OECD test methods is suggested to screen consumer products and mixtures for potential interaction with estrogen and androgen hormone receptors, in order to identify products that could have cumulative effects or support their safety concerning direct endocrine disruption capabilities.

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Total Effective Xenoestrogen Burden in Serum Samples and Risk for Breast Cancer in a Population-Based Multicase–Control Study in Spain

Cited by 49 publications

References 34 publications

Effects of Benzophenone-3 and Propylparaben on Estrogen Receptor–Dependent R-Loops and DNA Damage in Breast Epithelial Cells and Mice

Effects of Benzophenone-3 and Propylparaben on Estrogen Receptor–Dependent R-Loops and DNA Damage in Breast Epithelial Cells and Mice

Know thy unknowns: why we need to widen our view on endocrine disruptors

Endocrine Disruption by Mixtures in Topical Consumer Products

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