title: Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Fountain
authors.affiliation: 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.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Abernathy
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lonardo
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Shoshana E
authors.initials: SE
authors.lastname: Rothstein
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Dominello
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Yunker
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Shirish
authors.initials: S
authors.lastname: Gadgeel
authors.affiliation: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine , Detroit, MI , USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Joiner
authors.affiliation: 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.
authors.forename: Gilda G
authors.initials: GG
authors.lastname: Hillman
keywords: esophagitis; histopathology; radiation; radioprotection; soy isoflavones