Barcellos-Hoff M H
Life Sciences Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Cancer Res. 1993 Sep 1;53(17):3880-6.
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 gamma-radiation in the mammary gland of adult female BALB/c mice. Rapid induction of transforming growth factor beta (TGF beta) immunoreactivity was observed at 1 h post radiation. Extracellular and intracellular TGF beta 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 beta 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 beta, 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 beta may mediate the remodeling of the stromal extracellular matrix in the irradiated mammary gland.
关于辐射诱导的体内蛋白质表达知之甚少，早期分子事件与随后的组织修复、纤维化或致癌作用之间的关系也尚未得到充分评估。在本研究中，检测了电离辐射暴露后立即及短时间内乳腺中参与组织重塑的蛋白质表达。使用间接免疫荧光法，在成年雌性BALB/c小鼠乳腺中，对全身γ射线照射0、5或10 Gy后选定的抗原随时间的变化进行了追踪。辐射后1小时观察到转化生长因子β（TGFβ）免疫反应性迅速诱导。上皮周围基质鞘中的细胞外和细胞内TGFβ增加，分别通过与抗体CC(1 - 30)和LC(1 - 30)的免疫反应性得以证明。此外，细胞外和细胞内TGFβ在先前呈阴性的脂肪基质中意外表达。照射后这种升高的表达持续了7天。因此，对辐射暴露的早期反应是TGFβ的诱导，它在组织修复、生长和细胞外基质产生过程中介导无数事件。检测了辐射暴露后细胞外基质蛋白的分布随时间的变化。第1天时上皮周围基质中的胶原蛋白III免疫反应性降低。相比之下，第3天时脂肪基质中出现新的胶原蛋白III，上皮周围胶原蛋白III的丰度和强度均增加。到第7天时，脂肪基质中的胶原蛋白III表达消失，但上皮周围基质中的表达增强。在同一时期，上皮周围的基质胶原蛋白I免疫反应性变得弥散且可能减弱。纤连蛋白、层粘连蛋白和胶原蛋白IV的定位在整个时间过程中未发生变化。我推测辐射诱导的TGFβ可能介导受照射乳腺中基质细胞外基质的重塑。
