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Adult withdrawal of long-term Benzophenone-3 treatment induces regression of mammary ductal branching in a

Calista Busch1, Anastasia Kariagina1, Elena Morozova1

  • 1Department of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI, USA.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|January 18, 2025
PubMed
Summary

Benzophenone-3 (BP-3) exposure impacts mammary duct development differently based on diet. High-fat diets promote branching, while low-fat diets cause regression, linked to immune system changes.

Keywords:
Benzophenone-3Dietary fatIgf-1Immune polarizationMammary ductal developmentOxybenzone

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Area of Science:

  • Endocrinology
  • Toxicology
  • Immunology

Background:

  • Benzophenone-3 (BP-3), or oxybenzone, is a common sunscreen ingredient with potential endocrine-disrupting properties.
  • Previous research indicated BP-3's dual role in mammary tumorigenesis, influenced by dietary fat.
  • This study investigates BP-3's effects on mammary ductal development in a diet-dependent manner.

Purpose of the Study:

  • To examine the diet-dependent effects of Benzophenone-3 (BP-3) on mammary ductal development.
  • To investigate the role of immune cell populations in mediating BP-3's effects.
  • To assess the impact of BP-3 exposure and withdrawal on reproductive health.

Main Methods:

  • BALB/c mice were treated with BP-3 from puberty through adulthood, with subsequent withdrawal periods.
  • Dietary interventions included low-fat and high-fat conditions.
  • Mammary ductal development, Igf1 gene expression, and immune cell populations (T cells, macrophages) were analyzed.

Main Results:

  • Long-term BP-3 exposure followed by withdrawal led to ductal branching regression in low-fat diet mice, associated with increased Igf1 expression.
  • BP-3 treatment in high-fat diet mice increased ductal branching, which reversed upon BP-3 withdrawal.
  • A shift in mammary gland immune cell polarization from Th1/M1 to Th2/M2 was observed, correlating with diet.

Conclusions:

  • Dietary context significantly modulates the effects of Benzophenone-3 on mammary gland development.
  • Immune system alterations may underlie the diet-dependent toxicity of BP-3.
  • Findings suggest potential reproductive health risks associated with BP-3 exposure, necessitating further research and consideration of dietary factors.