Radioprotection of lung tissue by soy isoflavones.
BACKGROUND
Radiation-induced pneumonitis and fibrosis have restricted radiotherapy for lung cancer. In a preclinical lung tumor model, soy isoflavones showed the potential to enhance radiation damage in tumor nodules and simultaneously protect normal lung from radiation injury. We have further dissected the role of soy isoflavones in the radioprotection of lung tissue.


METHODS
Naive Balb/c mice were treated with oral soy isoflavones for 3 days before and up to 4 months after radiation. Radiation was administered to the left lung at 12 Gy. Mice were monitored for toxicity and breathing rates at 2, 3, and 4 months after radiation. Lung tissues were processed for histology for in situ evaluation of response.


RESULTS
Radiation caused damage to normal hair follicles, leading to hair loss in the irradiated left thoracic area. Supplementation with soy isoflavones protected mice against radiation-induced skin injury and hair loss. Lung irradiation also caused an increase in mouse breathing rate that was more pronounced by 4 months after radiation, probably because of the late effects of radiation-induced injury to normal lung tissue. However, this effect was mitigated by soy isoflavones. Histological examination of irradiated lungs revealed a chronic inflammatory infiltration involving alveoli and bronchioles and a progressive increase in fibrosis. These adverse effects of radiation were alleviated by soy isoflavones.


CONCLUSIONS
Soy isoflavones given pre- and postradiation protected the lungs against adverse effects of radiation including skin injury, hair loss, increased breathing rates, inflammation, pneumonitis and fibrosis, providing evidence for a radioprotective effect of soy.
Departments of *Radiation Oncology, †Immunology and Microbiology, ‡Pathology, and §Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan.
Gilda G
GG
Hillman
Vinita
V
Singh-Gupta
Fulvio
F
Lonardo
David J
DJ
Hoogstra
Lisa M
LM
Abernathy
Christopher K
CK
Yunker
Shoshana E
SE
Rothstein
Joseph
J
Rakowski
Fazlul H
FH
Sarkar
Shirish
S
Gadgeel
Andre A
AA
Konski
Michael C
MC
Joiner
D000505:Alopecia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D019587:Dietary Supplements; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007529:Isoflavones / Q000008:administration & dosage* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D017785:Photons / Q000009:adverse effects*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017564:Radiation Pneumonitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D013025:Glycine max / Q000737:chemistry
D007529:Isoflavones; D011837:Radiation-Protective Agents