Fountain Matthew D, Abernathy Lisa M, Lonardo Fulvio, Rothstein Shoshana E, Dominello Michael M, Yunker Christopher K, Chen Wei, Gadgeel Shirish, Joiner Michael C, Hillman Gilda G
Department of Immunology and Microbiology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA ; Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
Front Oncol. 2015 Oct 21;5:238. doi: 10.3389/fonc.2015.00238. eCollection 2015.
Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated.
C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by hematoxylin-eosin, Masson's Trichrome and Ki-67 staining at 1, 4, 10, and 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-αSMA and anti-CD45, respectively.
Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as 1 week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy.
Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy.
接受放射治疗的肺癌患者会出现急性食管炎和慢性纤维化,这是食管组织受到辐射损伤的结果。我们已经表明,大豆异黄酮可减轻辐射对正常肺脏毒性所致的肺炎和纤维化。本研究调查了大豆异黄酮对辐射诱导的食管炎组织病理学变化的影响。
对C57BL/6小鼠进行单次胸部10 Gy或25 Gy照射,并给予大豆异黄酮处理,持续16周。在放疗后1、4、10和16周,通过苏木精-伊红染色、Masson三色染色和Ki-67染色评估食管组织损伤情况。分别使用抗αSMA和抗CD45抗体通过免疫组织化学法测定对平滑肌细胞和白细胞浸润的影响。
辐射导致食管组织层增厚,而大豆异黄酮可使其显著减轻。主要的辐射改变包括黏膜上皮基底细胞肥大、黏膜肌层平滑肌细胞损伤以及固有层结缔组织中胶原纤维破坏伴白细胞浸润。这些影响在放疗后1周即可观察到,且在25 Gy的较高剂量下更为明显。大豆异黄酮在10 Gy和25 Gy剂量下均能限制辐射诱导的组织损伤程度。
大豆异黄酮对食管具有辐射防护作用,可减轻辐射损伤在食管多个组织层的早期和晚期影响。大豆可与放疗联合使用,以降低接受胸部放疗的肺癌患者食管炎的发生率和严重程度。