Abstract
Background
Benzophenone-3 is a putative endocrine disrupting chemical and common active ingredient in sunscreens and personal care products. 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 their potential in promoting breast cancer. We previously demonstrated promotion of mammary tumorigenesis by a diet high in saturated animal fat. This study examines the activity of benzophenone-3 in a dietary context to provide insight into its potential role in promoting breast cancer, and how diet might influence this.
Methods
Mammary tumorigenesis was studied in a BALB/c mouse Trp53-null transplantation model. Three-week-old mice were fed low-fat or high-fat diets, and at ten weeks of age were switched to high-fat or low-fat diets, respectively, while other mice were maintained continuously on low-fat diet. Mice additionally were treated continuously with or without benzophenone-3. The level of benzophenone-3 exposure yielded levels in urine similar to that observed in humans subjected to heavy topical exposure of benzophenone-3-containing commercial sunscreen.
Results
Benzophenone-3 had complex effects that were dependent upon diet and tumor histopathology. Benzophenone-3 was protective in regard to epithelial tumorigenesis in mice fed low-fat diet and was promotional for epithelial tumorigenesis in mice fed high-fat diet restricted to adulthood. It increased tumor cell proliferation, decreased tumor cell apoptosis, and increased tumor vascularity in a manner dependent on specific dietary regimen and tumor histopathology. Protective effects were not always concordant with a decrease in properties associated with tumor progression. Notably, although benzophenone-3 seemed protective for tumorigenesis in mice fed low-fat diet, spindle cell tumors that arose in these mice showed increased proliferation and decreased apoptosis.
Conclusions
Benzophenone-3 elicits promotional and protective effects on mammary tumorigenesis dependent upon diet and tumor histopathology. However, even in instances of an ostensibly protective effect, other parameters suggest potential for greater risk. 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 the context of varying diets.
Protective effects of some fruit juices with low-fat diet on rat testis damaged by carbon tetrachloride: A genetic and histological study