Biomedical Engineering Reference
In-Depth Information
Chapter 11
Zebrafish: A Predictive Model
for Assessing Cancer Drug-
Induced Organ Toxicity
Louis D'Amico 1 , Chunqi Li 1 , Elizabeth Glaze 2 , Myrtle Davis 2 ,andWenLinSeng 1
1 Phylonix, Cambridge, MA, USA
2 NCI, NIH, Bethesda, MD, USA
11.1 INTRODUCTION
In this study, we visually assessed acute zebrafish organ toxicity of five cancer drug
candidates: 17-DMAG, HDAC inhibitor X, paclitaxel, SMA-838, and zebularine.
To assess acute toxicity, we initially determined the lethal compound concentration
after treatment for 24 h. Zebrafish were then treated for 24 h with six drug
concentrations
LC 10 and effects on heart, central nervous system, liver, and
kidneymorphology, function, and organ-specific cell deathwere assessed. Based on
results for assessing organ morphology and function, we estimated the no observ-
able effect concentration (NOEC). Next, we assessed reversibility of toxic effects.
After treatment for 24 h, drugs were removed by washing zebrafish in fresh fish
water and incubating for an additional 48 h. Organ morphology and function were
then reassessed. Finally, results in zebrafish showed good correlation with available
results inmammals and humans. These results show that drugs can be added directly
tofishwaterandeffectsonmajororganscanbevisuallyassessedinthistransparent
animal.
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