Defining the Molecular and Cellular Basis of Toxicity Using Comparative Models

Ballatori, Nazzareno; Villalobos, Alice R

doi:10.1006/taap.2002.9488

Cited by 56 publications

(33 citation statements)

References 177 publications

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“…Starting in the mid 1990s C. elegans became a more widely-used model in the neurotoxicology community [3,29,31,33]. This was partly due to the simplicity of their nervous system, which is a relatively small neuronal network that is highly stereotypical from animal to animal [6].…”

Section: Overviewmentioning

confidence: 99%

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

McVey

Mink²,

Snapp³

et al. 2012

J Environ Anal Toxicol

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Section: Overviewmentioning

confidence: 99%

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

McVey

Mink²,

Snapp³

et al. 2012

J Environ Anal Toxicol

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“…Importantly, comparative sequences from evolutionarily distant species now have the potential to build a conceptual framework for interpretation of the mammalian sequences. This leads several authors to conclude that the comparative approach will be increasingly valued by the biomedical community in the postgenomic era (Ballatori and Villalobos, 2002;Dow and Davies, 2003). Comparative genomics of non-genetic species will be used to inform the function of gene products as well as their evolution.…”

Section: Role Of Non-genetic Organisms In the Post-genomics Era: Compmentioning

confidence: 99%

Molecular biology of ion motive proteins in comparative models

Wheatly

Gao

2004

Journal of Experimental Biology

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This article will review the utility of comparative animal models in understanding the molecular biology of ion transport. Due to the breadth of this field some 'disclaimers' need to be established up front. 'Comparative' will be defined as non-mammalian. 'Genetic species' will be defined as organisms that have been selected as models for genetic studies and for which the genome has been largely sequenced. 'Non-genetic species' will include other non-mammalian organisms. The review will be limited to ions that play a major role in extracellular (EC) ionoregulation (Na/K/Ca/Cl) and not to micronutrients (Fe) or heavy metals (Cd, Zn). The review will focus only on ion motive proteins that have been associated with vectorial transfer at epithelial tissues. The review is therefore intended as a guidepost to researchers new to the field as well as to inform biologists of the power of comparative genomics.

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“…Recently two alternative in vivo model systems, Caenorhabditis elegans (nematode) and Danio rerio (zebrafish) which were well known and used in the field of Developmental and Molecular Biology became noticed as potential promising test systems for hazard assessment (Avila et al, 2012;Ballatori, 2002;Boyd et al, 2016Boyd et al, , 2010Brannen et al, 2010;Hermsen et al, 2011;Leung et al, 2008;Panzica-Kelly et al, 2010;Dhawan et al, 1999;Selderslaghs et al, 2009Selderslaghs et al, , 2012. Both species share high genetic homology to man (~60% for nematodes and 70% for zebrafish), show cell biologically conserved molecular responses (like organ development, cell and tissue signaling etc.)…”

Section: Introductionmentioning

confidence: 99%

Application of Caenorhabditis elegans (nematode) and Danio rerio embryo (zebrafish) as model systems to screen for developmental and reproductive toxicity of Piperazine compounds

Rácz

Wildwater

Rooseboom

et al. 2017

Toxicology in Vitro

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A B S T R A C TTo enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement).In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This is because they often lack biotransformation capacity, multicellular or multi-organ complexity, for example, the hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms.To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode) and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals being considered for a new commercial application. Nematodes exposed to Piperazine and one of the analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental delays. Malformations and mortality in individual fish were also scored. Significant malformations were most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish.The results of the nematode and zebrafish studies were in alignment with data obtained from conventional mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems. The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications.

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Defining the Molecular and Cellular Basis of Toxicity Using Comparative Models

Cited by 56 publications

References 177 publications

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

Caenorhabditis elegans: An Emerging Model System for Pesticide Neurotoxicity

Molecular biology of ion motive proteins in comparative models

Application of Caenorhabditis elegans (nematode) and Danio rerio embryo (zebrafish) as model systems to screen for developmental and reproductive toxicity of Piperazine compounds

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