The zebrafish--Danio rerio--is a useful model for measuring the effects of small-molecule mitigators of late effects of ionizing irradiation.

Background/Aim: Use of zebrafish models may decrease the cost of screening new irradiation protectors and mitigators. Materials and Methods: Zebrafish (Danio rerio) models were tested for screening water-soluble radiation protectors and mitigators. Irradiation of embryos and monitoring survival, and measuring fibrosis of the caudal musculature of adults allowed for testing of acute and late effects, respectively. Results: Incubation of zebrafish embryos either before or after irradiation in ethyl pyruvate (1 mM) increased survival. Irradiation of adults to 15 to 75 Gy, delivered in single-fraction at 13 Gy/min, showed dose- dependent fibrosis at 30 days, quantitated as physiological decrease in swimming tail movement, and histopathological detection of collagen deposition in the dorsal musculature. Continuous administration of small-molecule radioprotector drugs in the water after irradiation reduced both acute and chronic injuries. Conclusion: The zebrafish is cost-effective for screening new radiation countermeasures. A major complication of ionizing irradiation exposure is fibrosis (1, 19, 58). Patients completing a course of fractionated radiotherapy for treatment of head and neck, thoracic, and abdominal malignancies demonstrate dose- dependent appearance of late effects within 6-24 months after irradiation (59-60). While acute effects of radiation are well- documented for both total body and organ-specific exposure, a latent period following resolution of the acute effects has been difficult to relate to the onset of late effects (3, 8, 10, 19). In the C57BL/6J mouse model of radiation pulmonary fibrosis, elevation of cytokines associated with the acute effects (TGFβ,