Muscular contractions in the zebrafish embryo are necessary to reveal thiuram-induced notochord distortions

Journal Article · Sat Apr 01 04:00:00 EST 2006 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2005.06.016· OSTI ID:20783450

Teraoka, Hiroki ^[1]; Urakawa, Satsuki ^[1]; Nanba, Satomi ^[1]; Nagai, Yuhki ^[1]; Dong, Wu ^[1]; Imagawa, Tomohiro ^[2]; Tanguay, Robert L ^[3]; Svoboda, Kurt ^[4]; Handley-Goldstone, Heather M ^[5]; Stegeman, John J ^[5]; Hiraga, Takeo ^[1]

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1. Department of Toxicology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu 069-8501 (Japan)
2. Department of Veterinary Anatomy, Faculty of Agriculture, Tottori University, Tottori (Japan)
3. Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States)
4. Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States)
5. Department of Biology, Woods Hole Oceanographic Institution, Woods Hole, MA 02543 (United States)

Dithiocarbamates form a large group of chemicals that have numerous uses in agriculture and medicine. It has been reported that dithiocarbamates, including thiuram (tetramethylthiuram disulfide), cause wavy distortions of the notochord in zebrafish and other fish embryos. In the present study, we investigated the mechanism underlying the toxicity of thiuram in zebrafish embryos. When embryos were exposed to thiuram (2-1000 nM: 0.48-240 {mu}g/L) from 3 h post fertilization (hpf) (30% epiboly) until 24 hpf (Prim-5), all embryos develop wavy notochords, disorganized somites, and have shortened yolk sac extensions. The thiuram response was specific and did not cause growth retardation or mortality at 24 hpf. The thiuram-dependent responses showed the same concentration dependence with a waterborne EC{sub 5} values of approximately 7 nM. Morphometric measurements revealed that thiuram does not affect the rate of notochord lengthening. However, the rate of overall body lengthening was significantly reduced in thiuram-exposed animals. Other dithiocarbamates, such as ziram, caused similar malformations to thiuram. While expression of genes involved in somitogenesis was not affected, the levels of notochord-specific transcripts were altered after the onset of malformations. Distortion of the notochord started precisely at 18 hpf, which is concomitant with onset of spontaneous rhythmic trunk contractions. Abolishment of spontaneous contractions using tricaine, {alpha}-bungarotoxin, and a paralytic mutant sofa potato, resulted in normal notochord morphology in the presence of thiuram. These results indicate that muscle activity is necessary to reveal the underlying functional deficit and suggest that the developmental target of dithiocarbamates impairs trunk plasticity through an unknown mechanism.

• OSTI ID: 20783450
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 212; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGRICULTURE
DISULFIDES
DRUGS
EMBRYOS
FERTILIZATION
MALFORMATIONS
MEDICINE
MORPHOLOGY
MORTALITY
MUTANTS
PESTICIDES
PLASTICITY
POTATOES
TOXICITY