In this high-Altmetric scoring Oncotarget paper, researchers examined the in vivo activity of benzophenone-3—a common ingredient in sunscreen and an endocrine-disrupting chemical—in mice within a dietary context to determine its potential role in promoting breast cancer.
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Benzophenone-3 (BP-3 or oxybenzone) has been identified as a known endocrine-disrupting chemical (EDC) and, alarmingly, it is a common ingredient in many modern brands of sunscreen. BP-3 is also present in household dust, fish lipids, and due to its widespread human use, the water environment. Previous studies have shown that environmental toxins and estrogenic chemicals have emerged as potential culprits in the promotion of breast cancer. BP-3 in particular has been known to have estrogenic and anti-estrogenic properties.
Researchers, from the Breast Cancer and the Environment Research Program at Michigan State University, authored a paper titled: “Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent.” This study currently presents with an Altmetric Attention score of 65.
“We [previously] demonstrated enhancement of mammary tumorigenesis by a diet high in saturated animal fat (HFD) [5–8]. Thus, examination of the activity of EDCs in a dietary context may provide additional insight into the potential role of EDCs in promoting breast cancer.”
The researchers previously demonstrated the effects of a high-fat diet (HFD) in breast cancer. In the current study, they examined BP-3 in mice under three dietary conditions: mice fed a life-long low-fat diet (LFD), mice fed a low-fat diet during puberty and then a high-fat diet in adulthood (LFD-HFD), and mice fed a high-fat diet during puberty and then a low-fat diet in adulthood (HFD-LFD).
Using the Trp53–null transplantation model of basal-like breast cancer, both pubertal and adult mice were first placed on a LFD or HFD. Sample mice were injected with BP-3, ovariectomized, given time for recovery and the natural dissipation of endogenous hormones, and treated with 17β-estradiol (E2; estrogen) for five days.
“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. Thus, it is logical to test their individual and combined effects on mammary tumorigenesis.”
The mice in both variations of the HFD and LFD were fed their initial diet from three to 10 weeks of age, and then switched to the other diet. Half of the mice were injected with BP-3 and the other half were used as the control groups.
“As BP-3 has known estrogenic and anti-estrogenic properties , and our studies herein show BP-3 enhanced estrogen-stimulated mammary proliferation, we examined estrogen levels in plasma from sacrificed tumor-bearing mice.”
“We found that BP-3 had complex effects that were dependent upon dietary regimen and tumor histopathology.”
Consistent with the researchers’ earlier studies, most of the tumors in mice were epithelial in composition and some were spindle cell carcinomas. The LFD-HFD combination resulted in an increased proportion of spindle cell tumors compared to the LFD, however, the proportion of epithelial versus spindle cell tumors was also increased by BP-3 treatment in mice fed the LFD-HFD.
“BP-3 did not significantly alter apoptosis, except for spindle cell tumors arising in mice fed LFD (Figure 6). Apoptosis in spindle cell tumors from LFD + BP-3 mice was reduced by half compared to those from LFD mice (Figure 6B).”
“Kaplan-Meier analysis revealed that BP-3 reduced tumorigenesis of epithelial tumors in mice fed LFD (Figure 3A). On the other hand, consistent with the increased proportion of epithelial tumors, BP-3 was promotional for epithelial tumorigenesis in mice fed LFD-HFD (Figure 3C), while reducing spindle cell tumorigenesis (Figure 3D).”
Researchers saw that BP-3 treatment increased the number of lesions only in mice fed the HFD-LFD. Proliferation in all dietary groups was increased by BP-3 treatment. An analysis of variance (ANOVA) test found that BP-3 treatment only produced a significant effect on proliferation in the mammary glands of 26-week old mice.
“We observed a modest, but statistically significant, reduction in estrogen levels by BP-3 treatment of mice fed HFD-LFD.”
Importantly, the researchers note that, in this study and others, they observed a “pubertal window of susceptibility,” reinforcing that puberty is a highly sensitive window of time for adverse exposures. Ultimately, the team found that BP-3 enhances estrogen-stimulated mammary gland proliferation in pubertal mice fed a HFD.
“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.”
Collectively, the researchers’ findings suggest that exposure to BP-3 may have adverse consequences in mammary tumorigenesis and that it has differential effects among the three dietary regimens studies.
“Benzophenone-3 increased tumor cell proliferation, decreased tumor cell apoptosis, and increased tumor vascularity dependent on specific dietary regimen and tumor histopathology.”
“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.”
“Regarding BP-3, it will be valuable to eventually explore pubertal versus adult exposure to BP-3 on a constant diet regimen.”
Click here to read the full scientific study, published in Oncotarget.
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