Radiation-Induced Toxicity and Radiation Response Modifiers in Zebrafish - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 285

Chapter 21

Radiation-Induced Toxicity
and Radiation Response
Modifiers in Zebrafish

Adam P. Dicker 1 , Gabor Kari 1 , and Ulrich Rodeck 1,2
1 Department of Radiation Oncology, Thomas JeffersonUniversity, Philadelphia, PA, USA
2 Department of Dermatology, Thomas Jefferson University, Philadelphia, PA, USA

21.1 INTRODUCTION

Radiation therapy (RT) remains a key therapeutic option for a wide range of neoplastic
diseases, either alone or in combination with other treatment modalities. However, the
radiation doses that can be safely administered are often lower than those required to
eradicate tumor cells. This is due in large part to “collateral damage” by radiation, that is,
toxicity to normal cells and tissues in the radiation field. The normal tissues most
relevent to radiation toxicity typically contain epithelial cells with high rates of turnover
including the lining of the gastrointestinal tract and the skin. Existing radiation
protectors including the FDA-approved amifostine (Brizel, 2007), sucralfate (Hovdenak
et al., 2005), and mesalazine (Sanguineti et al., 2003) are of limited utility in protecting
these normal tissues against radiation effects primarily due to their own toxicity.
The identification and functional exploration of novel radioprotective com-
pounds critically depend on performing studies in whole animals because the
interplay of several cell types is likely to contribute to both radiation toxicity and
radiation protection (Stone et al., 2003; Burdelya et al., 2006). In recognition of this
requirement, many studies have been done in higher vertebrates such as mice. In the
following, we will describe the use of zebrafish embryos as a complementary system
to identify targeted agents that interfere with select signaling intermediaries and
radioprotect the whole organism and/or specific organ systems.