In vivo 3D analysis of systemic effects after local heavy-ion beam irradiation in an animal model.

Kazuhiro Nagata ,Hiroki Oota,Yasuhiko Kobayashi,Toshiyuki Nishimaki,Tomoo Funayama,Kento Igarashi,Motoyuki Ogawa,Hiroshi Itoh,Natsumaro Kutsuna,Chika Hashimoto,Atsunori Oga,Shoji Oda,Hisako Oonishi,Tomomi Watanabe-Asaka,Takafumi Katsumura,Kousaku Ohta,Michiyo Suzuki,K Itoh ,K Ikemoto ,Tomoyuki Yasuda ,Hiroshi Mikami

doi:10.1038/srep28691

Abstract

Radiotherapy is widely used in cancer treatment. In addition to inducing effects in the irradiated area, irradiation may induce effects on tissues close to and distant from the irradiated area. Japanese medaka, Oryzias latipes, is a small teleost fish and a model organism for evaluating the environmental effects of radiation. In this study, we applied low-energy carbon-ion (26.7 MeV/u) irradiation to adult medaka to a depth of approximately 2.2 mm from the body surface using an irradiation system at the National Institutes for Quantum and Radiological Science and Technology. We histologically evaluated the systemic alterations induced by irradiation using serial sections of the whole body, and conducted a heart rate analysis. Tissues from the irradiated side showed signs of serious injury that corresponded with the radiation dose. A 3D reconstruction analysis of the kidney sections showed reductions in the kidney volume and blood cell mass along the irradiated area, reflecting the precise localization of the injuries caused by carbon-beam irradiation. Capillary aneurysms were observed in the gill in both ventrally and dorsally irradiated fish, suggesting systemic irradiation effects. The present study provides an in vivo model for further investigation of the effects of irradiation beyond the locally irradiated area.

Highlights

Stresses such as chemicals in addition to radiation[22,23]
We expected that each medaka fish would receive dorsal irradiation (DR) or ventral irradiation (VR) according to its alignment
For the whole-body analysis of serial sections, we calculated that approximately 5,000 serial sections at a thickness of 5 μm would need to be cut from the head to the tail

Summary

Introduction

Stresses such as chemicals in addition to radiation[22,23]. Several medaka strains with mutations in the chromatophore allow for direct observations of the body’s interior using imaging or videotaping[24]. Medaka is small enough that it can be used to examine the acute somatic effects induced at the cellular level in all tissues. We established experimental procedures to locally irradiate adult medaka fish to a depth of approximately 2.2 mm from the body surface by using a heavy-ion beam irradiation system at National Institutes for Quantum and Radiological Science and Technology (QST) in Takasaki. We evaluated the systemic alterations induced by irradiation in serial sections of the whole body, and we performed heart rate analysis after the irradiation. We found evidence of oedema in capillaries in both the irradiated and non-irradiated areas. These observations suggest that the systemic effects are caused by local irradiation

Methods

Results

Conclusion