Dysfunction of Cardiovascular and Pharyngeal Development and Lethality Following Maternal Exposure to Radiation

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  • SHOJI Shuneki
    Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University
  • SHOJI Isao
    The Ohio State University, Columbus, OH, USA
  • SHOJI Toshihiro
    Vanderbilt University, Nashville, TN, USA

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  • 放射線被ばくと心臓血管系などの疾患およびその障害・致死などとの関連性

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Abstract

Cardiovascular diseases are the most common birth defects and adult diseases requiring medical and therapeutic intervention. In order to collect basic data for prevention of, as well as safety and therapeutic applications in, diseases related to environmental stresses, the biologically unique effects of chemical agents and radiation exposure need to be evaluated. The focus of this study is the abnormal development of the arterial pole of the heart and pharyngeal arch following maternal stress exposure to a chemical and ionizing radiation.<br>Pregnant rodents were given either chemicals or ionizing radiation, and we report on the relationships between each exposure group and subsequently observed embryonic lethality as well as external and visceral defects, especially craniofacial and cardiovascular, on day 18 of gestation. We observed a high incidence of teratogenesis, especially cardiovascular, pharyngeal and facial anomalies, in both treated groups. These results indicate sensitivity to chemicals and ionizing radiation exposures in fetuses leading to DNA damage, embryonic lethality, dysfunction of neural crest cells and pharynx development, which form neurocristopathy syndrome and neurocristopathy-induced cardiovascular and pharyngeal syndrome, respectively. The most common cardiovascular defects involved septation and alignment of the arterial pole of the heart. Particularly, craniofacial and cardiac outflow tract defects, including tetralogy of Fallot, atrioventricular septal defects and aortic arch anomalies noted following exposure, were quite similar to those found in studies of avian neural crest ablation model and to human syndromes.<br>We have previously studied teratogenesis and cardiovascular anomalies following similar maternal environmental stress exposure. It has shown that cardiovascular system diseases and tumorigenesis are some of the most common causes of sufferings in Hiroshima atomic bomb survivors and in their ultimate mortality. Studies were done on the role of neural crest cells in the structural development of the arterial pole by using several different animal models of human heart defects. Affected neural crest and neural crest cells that migrate to the pharynx and cardiovascular system and interfere with various developmental processes in the heart and pharynx are essential for abnormal craniofacial and cardiovascular development, as such cells disrupt signaling gene and transcription factors in the pharynx and cardiovascular system. This animal model is expected to contribute in investigating the mechanism of such dysfunction in neural crest and heart field in human syndromes and diseases, as well as their relative biological effectiveness.

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