Abstract
We previously found benzophenone-3, an endocrine disrupting chemical and common sunscreen ingredient, has promotional and protective effects on mammary tumorigenesis dependent upon dietary fat. The current study examines mammary correlates to the protective effect of benzophenone-3 in mice fed low-fat diet versus the promotional effect in mice fed high-fat diet during adulthood. Benzophenone-3 treatment of mice fed low-fat diet resulted in broad activation of Th1, Th2, and Th17 cells, a shift toward M2 macrophage polarization, and elevated Areg, Ereg, and TGFa RNAs. Benzophenone-3 treatment in mice fed adult high-fat diet resulted in decreased Tc cells, and elevated Rankl RNA. Mice fed adult high-fat diet by itself showed a shift toward M2 macrophage polarization and elevated Areg and Egf RNAs. The tumor protective effect of benzophenone-3 in low-fat diet mice plausibly results from heightened Th activity with expression of IL-21 sparing Tc activity. The tumor promoting effect of benzophenone-3 in mice fed adult high-fat diet plausibly results from reduced Tc activity and increased RANKL expression interacting with high-fat diet increased expression of mammary growth factors and M2 macrophage polarization. Dietary fat and benzophenone-3 have immunomodulatory consequences that may interact in affecting mammary tumorigenesis in either a protective or promotional fashion.