Simulated galactic cosmic radiation (GCR)-induced expression of Spp1 coincide with mammary ductal cell proliferation and preneoplastic changes in ApcMin/+ mouse

Abstract

Female astronauts inevitably exposed to galactic cosmic radiation (GCR) are considered at a greater risk for mammary cancer development. The purpose of this study is to assess the status of mammary cancer-associated preneoplasia markers after GCR and γ-ray irradiation using a mouse model of human mammary cancer. Female ApcMin/+ mice were irradiated to 50 cGy of either γ-ray (137Cs) or full-spectrum simulated galactic cosmic radiation (GCR) (33-beam), and at 110 – 120 days post-irradiation mice were euthanized, and normal-appearing mammary tissues were analyzed for histological and molecular markers of preneoplasia. Whole-mount staining, hematoxylin and eosin-based histological assessment, and Cyclin D1 immunohistochemistry (IHC) were performed to analyze ductal outgrowth and cell proliferation. Additionally, mRNA expression of known mammary preneoplasia markers (Muc1, Exo1, Foxm1, Depdc1a, Nusap1, Spp1, and Rrm2) was analyzed using qPCR, and their respective protein expression was validated using immunohistochemistry. A significant increase in ductal outgrowth and cell proliferation in mammary tissues of GCR-irradiated mice was noted which indicates a higher risk of mammary cancer, relative to γ-rays. Increased mRNA and protein expression of Spp1 was observed in the GCR group, relative to γ-rays. This study demonstrates the plausibility of Spp1 as a preneoplasia marker in the early detection of mammary cancer after space radiation exposure.