Biomedical Engineering Reference
In-Depth Information
Figure 21.1 Morphological and functional consequences of radiation exposure of zebrafish embryos.
(a) Characteristic dorsal curvature of body axis (“curly-up”) observed at 48hpf. (b) AO staining of
irradiated fish to detect apoptotic cells. The area used for quantitative analysis of AO staining at 30hpf
(6 h post radiation) is boxed and magnified. (c) PED6 staining of the gastrointestinal tract. Reduced
fluorescence and impaired gastrointestinal lumen formation is apparent in irradiated fish.
(d) Fluorescent dextran retention upon radiation exposure of zebrafish embryos. The dye is injected
intracardially at 72hpf and the decrease in signal over time (1 and 24 h post radiation) is monitored in the
cardiac area (as highlighted). Representative examples of control and irradiated fish showing dye
retention are shown. All experiments are typically performed on embryos irradiated at 24hpf. Note that
different radiation doses are used in different functional testing scenarios to enhance the sensitivity of
identifying potential radiation protectors.
21.6 RADIATION-ASSOCIATED GASTROINTESTINAL
TOXICITY
Damage to the small and large intestines is a major concern for the treatment of many
abdominal malignancies with radiation therapy. To investigate gastrointestinal
toxicity and the effects of radiation protectors on this phenomenon in zebrafish
embryos, several methods have proven informative. Perhaps the simplest way to
assess overall gastrointestinal function is to score “long-term” (up to 15 dpf) survival
of fish larvae irradiated with 15 Gy. Fish larvae become dependent on external food
sources at approximately 6 dpf when the contents of the yolk sac are depleted.
Significant functional damage to the gastrointestinal systemwill thus lead to death by
starvation within 10 dpf. Conversely, survival of fish beyond 2 weeks indicates
establishment of a functionally adequate gastrointestinal system among other organ
sites. Fish irradiated with 15 Gy do not survive beyond 14 dpf.
The effect of radiation on gastrointestinal function and lumen formation can be
further monitored by using the fluorescent reporter PED6 (Ho et al., 2004) that is
metabolized and excreted through the gastrointestinal system. Fluorescencemicroscopy
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