Evaluation of the developmental toxicity of thalidomide using frog embryo teratogenesis assay?Xenopus (FETAX): biotransformation and detoxification

Fort, Douglas J.; Stover, Enos L.; Bantle, John A.; Finch, Robert A.

doi:10.1002/(sici)1520-6866(2000)20:1<35::aid-tcm4>3.0.co;2-i

Cited by 34 publications

(17 citation statements)

References 34 publications

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“…These limitations can be partially overcome using an in vitro metabolic activation system, where test compounds are pretreated with activated rat liver microsomes (Fort et al, 1988). Using this pretreatment procedure, the teratogenic risk of proteratogenic compounds, such as thalidomide and aflatoxins, can be accurately assessed (Fort et al, 2000;Vismara and Caloni, 2007). Taken together, Xenopus represents a promising bioassay system in the drug discovery and development process that will complement cell culture assays, and in vivo experiments in mice.…”

Section: Assessing Toxicity and Teratogenicitymentioning

confidence: 99%

Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus

Wheeler

Brändli

2009

Developmental Dynamics

159

131

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Chemical genetics uses small molecules to modulate protein function and, in principle, has the potential to perturb any biochemical event in a complex cellular context. The application of chemical genetics to dissect biological processes has become an attractive alternative to mutagenesis screens due to its technical simplicity, inexpensive reagents, and low-startup costs. In vertebrates, only fish and amphibians are amenable to chemical genetic screens. Xenopus frogs share a long evolutionary history with mammals and so represent an excellent model to predict human biology. In this review, we discuss the lessons learned from chemical genetic studies carried out in zebrafish and Xenopus. We highlight how Xenopus can be employed as a convenient first-line animal model at various stages of the drug discovery and development process and comment on how they represent much-needed tools to bridge the gap between traditional in vitro and preclinical mammalian assays in biomedical research and drug development. Developmental

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Section: Assessing Toxicity and Teratogenicitymentioning

confidence: 99%

Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus

Wheeler

Brändli

2009

Developmental Dynamics

159

131

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“…Ten years of validation studies suggest that the true value of the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) model most likely lies in the versatility and utility of the model system. The FETAX model, or modifications thereof has been used to screen chemicals and prioritize discovery-level products, 1 evaluate modes of biotransformation, detoxification and mechanisms of action, 2 -14 serve as a model of limb development, 14,15 evaluate the impact of chemicals on thyroid function, 16,17 assess nutritional essentiality and toxicity of trace elements, 18 -23 evaluate environmental samples for potential effects on amphibian populations 24,25 and study mixture toxicity and structure-activity relationships. 26 -30 Thus, FETAX represents one of the most extensively validated alternative developmental toxicity test systems.…”

Section: Introductionmentioning

confidence: 99%

Enhancing the predictive validity of Frog Embryo Teratogenesis Assay—Xenopus (FETAX)

Fort

Paul

2002

J of Applied Toxicology

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Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a 4-day, alternative developmental toxicity assay designed to pre-screen chemicals and environmental mixtures. An approach used in the scoring of FETAX results, which focuses on the determination of characteristic abnormalities induced by a given test material, was used to evaluate results from previous validation efforts. Characteristic abnormalities are induced specifically by exposure to a given test material and are determined by the relationship between concentration and the response induced and the change in severity of response. Use of this approach eliminates non-specific effects that alter numerical endpoints, reduces intralaboratory variability, reduces the number of equivocal test results (gray area), helps to determine specific syndromes associated with teratogen exposure and, in some instances, increases the predictability of FETAX. In an effort to evaluate this approach, a 12-compound validation study that produced a relatively high degree of equivocal FETAX results was re-evaluated using the characteristic malformation criteria. Data were evaluated for repeatability, predictability and variability. Results from this study indicated that this scoring approach increased repeatability, test endpoint precision and predictability.

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“…The FETAX testing was conducted as described previously [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Groups of 20 normally developing blastula-stage embryos were placed in 60-mm covered plastic petri dishes containing various control or treatment solutions.…”

Section: Aqueous Samples With Fetax Testsmentioning

confidence: 99%

Progress Toward Identifying Causes of Maldevelopment Induced in Xenopus by Pond Water and Sediment Extracts From Minnesota, Usa

Fort¹,

Rogers²,

Copley³

et al. 1999

Environ Toxicol Chem

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In previously conducted laboratory studies with the South African clawed frog (Xenopus laevis), pond water and sediment samples collected from various sites in Minnesota, USA, were demonstrated to have the potential to induce a variety of developmental abnormalities, including early embryo-larval maldevelopment, abnormal limb development, and disruption of metamorphosis. The results of exposure of X. laevis to suspect pond water and sediment samples supported the hypothesis that these samples were capable of inducing these abnormalities as the result of either the presence of developmental toxicants or the absence of essential micronutrients. Physicochemical characterization of the causes of abnormal frog embryo-larval and limb development were performed using the frog embryo teratogenesis assay-Xenopus (FETAX). Specific compounds were subsequently identified within the complex mixture fractions and tested by dilution in a control solution and native reference water using both the 4- and 30-d treatment protocols. Results from these studies suggested that a complex mixture of both naturally occurring and man-made compounds was primarily responsible for the effects observed in X. laevis. The potency of several compounds was also enhanced by the site water, thus indicating that the water matrix deserves consideration as a contributing factor for both laboratory and field studies.

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Evaluation of the developmental toxicity of thalidomide using frog embryo teratogenesis assay?Xenopus (FETAX): biotransformation and detoxification

Cited by 34 publications

References 34 publications

Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus

Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus

Enhancing the predictive validity of Frog Embryo Teratogenesis Assay—Xenopus (FETAX)

Progress Toward Identifying Causes of Maldevelopment Induced in Xenopus by Pond Water and Sediment Extracts From Minnesota, Usa

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