Development of preventive method of ischemia induced by radiation therapy

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Radiation science
• Research Institution: The University of Tokyo
• Principal Investigator: SUZUKI Takahiko The University of Tokyo, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (10171224)
• Co-Investigator(Kenkyū-buntansha): HOSOI Yoshio The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50238747)
• Project Period (FY): 2004 – 2005
• Keywords: cardiomyocytes / radiation (X-ray) / endothelin / ischemia / heart / gene expression / rat

Research Abstract

There are reports that the radiation therapy to patients with lung cancers causes strictures of coronary artery (cardiac ischemia). However, the mechanism of this side effect of radiation therapy has not been cleared yet. This study was aimed to clarify the role of endothelin (ET), which is a strong vasoconstrictor, in the radiation induced strictures of coronary artery. ET is known to be synthesized and secreted not only by endothelial cells but also by cardiac myocytes. Therefore, we first tested whether the radiation caused ET gene expression or not using cultured cardiac myocytes. Five-days cultured cardiac myocytes were exposed to X-ray (2 to 50Gy). Over 10Gy X-ray induced increase in ET gene expression about 280% during 2 to 8 hours after radiation. However, we could not detect ET peptide in the culture medium measured with ELISA system. Small amount of ET peptide was detected in the cardiac myocytes which were exposed to 2 0Gy of X-ray. This suggested that X-ray radiation induce d increase in ET expression, but this effect was not so strong. Next, we investigated whether X-ray exposure induced ET expression or not at in vivo. Three-day old rats were anesthetized and chest area of the rats was exposed to 20Gy of X-ray. mRNA was extracted and the ET gene expression was estimated by quantitative RT-PCR. As the result, ET gene expression was increased by radiation similar to the in vitro studies. However, ET peptide was not detected in the cardiac tissues. These results suggest that ET gene expression is increased by radiation exposure in the cardiac myocytes not only in vitro but also in vivo. It is not clear that ET peptide is increased in the cardiac tissues by radiation exposure. However, there may be a possibility that increased gene expression of ET results increase in ET peptide in the patients' hearts caused by radiation therapy. Therefore, pre-administration of ET receptor antagonist may be a useful preventive method of cardiac ischemia induced by radiation therapy.