Medium- and high-throughput screening of neurotoxicants using C. elegans

被引:72
作者
Boyd, Windy A. [2 ]
Smith, Marjolein V. [3 ]
Kissling, Grace E. [1 ]
Freedman, Jonathan H. [1 ,2 ]
机构
[1] NIEHS, Mol Toxicol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA
[2] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA
[3] SRA Int, Res Triangle Pk, NC 27709 USA
关键词
C; elegans; Neurotoxicology; High-throughput screening; Toxicant; NEMATODE CAENORHABDITIS-ELEGANS; END-POINTS; BEHAVIOR; TOXICITY; SYSTEM; PHARYNX; DEGENERATION; REPRODUCTION; EXPRESSION; SEROTONIN;
D O I
10.1016/j.ntt.2008.12.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The U.S. National Toxicology Program, the U.S. Environmental Protection Agency, and other national and international agencies are committing significant resources towards the development of alternative species to be used as replacements for mammalian models in toxicological studies. Caenorhabditis elegans is a well-characterized soil nematode that is becoming a useful model in the assessment of neurotoxicants. To determine the effects of potential neurotoxicants on C elegans, four medium-throughput (feeding, growth, reproduction and locomotion) and two high-throughput (growth and reproduction) assays have been developed. Three of these assays use the COPAS Biosort, a flow cytometer capable of rapidly measuring thousands of nematodes in minutes. Medium-through put feeding, growth, and reproduction assays were used to assess the toxicity of eight suspected neurotoxicants. For several of the neurotoxicants examined, significant effects were observed at similar concentrations between assays. High-throughput reproduction and growth assays were used to estimate the toxicity of thousands of chemicals in two libraries. These assays will prove useful in evaluating the role of alternative toxicological models in tiered toxicity testing of thousands of chemicals. Published by Elsevier Inc.
引用
收藏
页码:68 / 73
页数:6
相关论文
共 70 条
[1]   PHARYNX OF CAENORHABDITIS ELEGANS [J].
ALBERTSON, DG ;
THOMSON, JN .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES, 1976, 275 (938) :299-&
[2]  
Altun Z.F., 2002, WormAtlas
[3]   Assessing behavioral toxicity with Caenorhabditis elegans [J].
Anderson, GL ;
Cole, RD ;
Williams, PL .
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, 2004, 23 (05) :1235-1240
[4]   Assessment of sublethal endpoints for toxicity testing with the nematode Caenorhabditis elegans [J].
Anderson, GL ;
Boyd, WA ;
Williams, PL .
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, 2001, 20 (04) :833-838
[5]   Food transport in the C-elegans pharynx [J].
Avery, L ;
Shtonda, BB .
JOURNAL OF EXPERIMENTAL BIOLOGY, 2003, 206 (14) :2441-2457
[6]  
AVERY L, 1993, GENETICS, V133, P897
[7]   EFFECTS OF STARVATION AND NEUROACTIVE DRUGS ON FEEDING IN CAENORHABDITIS-ELEGANS [J].
AVERY, L ;
HORVITZ, HR .
JOURNAL OF EXPERIMENTAL ZOOLOGY, 1990, 253 (03) :263-270
[8]  
Avery Leon., 1997, Cold Spring Harbor Monograph Archive, V33, P679
[9]   Using machine vision to analyze and classify Caenorhabditis elegans behavioral phenotypes quantitatively [J].
Baek, JH ;
Cosman, P ;
Feng, ZY ;
Silver, J ;
Schafer, WR .
JOURNAL OF NEUROSCIENCE METHODS, 2002, 118 (01) :9-21
[10]  
Bany IA, 2003, J NEUROSCI, V23, P8060