Little is known about radiation-induced protein expression in vivo nor has the relationship between early molecular events and subsequent tissue repair, fibrosis, or carcinogenesis been fully appraised. In this study, expression of proteins involved in tissue remodeling was examined in mammary gland immediately and shortly after ionizing radiation exposure. Using indirect immunofluorescence, selected antigens were followed as a function of time after 0, 5, or 10 Gy of whole body γ-radiation in the mammary gland of adult female BALB/c mice. Rapid induction of transforming growth factor β (TGF β) immunoreactivity was observed at 1 h post radiation. Extracellular and intracellular TGF β increased in the periepithelial stromal sheath as evidenced by immunoreactivity with antibodies CC(1–30) and LC(1–30), respectively. Furthermore, both extracellular and intracellular TGF β were unexpectedly expressed in the previously negative adipose stroma. Elevated expression persisted for 7 days after irradiation. Thus an early response to radiation exposure is the induction of TGF β, which mediates myriad events during tissue repair, growth, and extracellular matrix production. The distribution of extracellular matrix proteins was examined as a function of time post radiation exposure. Collagen III immunoreactivity decreased in the periepithelial stroma at day 1. In contrast, at day 3 collagen III was newly evident in the adipose stroma, and periepithelial collagen III had increased in both abundance and intensity. By day 7 collagen III expression in the adipose stroma had resolved but was enhanced in the periepithelial stroma. Over this same period stromal collagen I immunoreactivity surrounding the epithelium became diffuse and possibly diminished. Fibronectin, laminin, and collagen IV localization were unchanged over the time course. I postulate that radiation-induced TGF β may mediate the remodeling of the stromal extracellular matrix in the irradiated mammary gland.
This work was supported by National Cancer Institute Grant CA51841 and the Office of Health and Environmental Research, Health Effects Research Division, of the United States Department of Energy under Contract DE-AC-03-76SF00098.