Journal of Radiation Oncology

, Volume 6, Issue 3, pp 307–315 | Cite as

Radiation injury to cardiac arteries and myocardium is reduced by soy isoflavones

  • Michael M. Dominello
  • Matthew D. Fountain
  • Shoshana E. Rothstein
  • Alexa C. Cannon
  • Lisa M. Abernathy
  • David Hoogstra
  • Wei Chen
  • Michael C. Joiner
  • Gilda G. HillmanEmail author
Original Research



The negative effects of incidental radiation on the heart and its vessels, particularly in the treatment of locally advanced non-small cell lung cancer, esophageal cancer, left-sided breast cancer, and lymphoma, are known. Late cardiac events induced by radiotherapy including coronary artery disease, ischemia, congestive heart failure, and myocardial infarction can manifest months to years after radiotherapy. We have previously demonstrated that soy isoflavones mitigate inflammatory responses induced in lungs by thoracic irradiation resulting in decreased vascular damage, inflammation, and fibrosis. In the current study, we investigate the use of soy isoflavones to protect cardiac vessels and myocardium from radiation injury.


Mice received a single dose of 10-Gy thoracic irradiation and daily oral treatment with soy isoflavones. At different time points, hearts were processed for histopathology studies to evaluate the effect of soy isoflavones on radiation-induced damage to cardiac vessels and myocardium.


Radiation damage to arteries and myocardium was detected by 16 weeks after radiation. Soy isoflavones given in conjunction with thoracic irradiation were found to reduce damage to the artery walls and radiation-induced fibrosis in the myocardium.


Our histopathological findings suggest a radioprotective role of soy isoflavones to prevent cardiac injury. This approach could translate to the use of soy isoflavones as a safe complement to thoracic radiotherapy with the goal of improving the overall survival in patients whose cancer has been successfully controlled by the radiotherapy but who otherwise succumb to heart toxicity.


Radiation Soy isoflavones Heart arteries Myocardium Radioprotection 



This work was supported by RTOG CCOP funded through U10CA037422 by the National Cancer Institute, the National Cancer Institute grant R21CA155518, Wayne State University Boost grant, and Wayne State University Research Bridge fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or National Institutes of Health. We thank Christopher Yunker for his excellent technical assistance, Kali Hankerd for data organization, and Dr. Lonardo from the Pathology Department at Wayne State University for his guidance in histology. The Microscopy, Imaging and Cytometry Resources Core is supported, in part, by the NIH Center grant P30 CA022453 to the Karmanos Cancer Institute at Wayne State University and the Perinatology Research Branch of the National Institutes of Child Health and Development at Wayne State University.

Compliance with ethical standards


This study was funded by RTOG CCOP funded through U10CA037422 by the National Cancer Institute, the National Cancer Institute grant R21CA155518, Wayne State University Boost grant, and Wayne State University Research Bridge fund, the USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or National Institutes of Health.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and the use of animals were followed. The animal protocol was approved by Wayne State University Animal Investigation Committee. Mice were housed and handled in facilities accredited by the American Association for the Accreditation of Laboratory Animal Care. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Informed consent

Statement of informed consent was not applicable since the manuscript does not contain any patient data.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Michael M. Dominello
    • 1
  • Matthew D. Fountain
    • 1
    • 2
  • Shoshana E. Rothstein
    • 1
  • Alexa C. Cannon
    • 1
  • Lisa M. Abernathy
    • 1
    • 2
    • 3
  • David Hoogstra
    • 1
  • Wei Chen
    • 1
  • Michael C. Joiner
    • 1
  • Gilda G. Hillman
    • 1
    • 2
    Email author
  1. 1.Department of Oncology, Division of Radiation Oncology, Karmanos Cancer InstituteWayne State University School of MedicineDetroitUSA
  2. 2.Department of Immunology & Microbiology, Karmanos Cancer InstituteWayne State University School of MedicineDetroitUSA
  3. 3.Department of Microbiology and ImmunologyIndiana University School of Medicine at Notre DameSouth BendUSA

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