ATLA 41.3, July 2013

//ATLA 41.3, July 2013

Volume 41, issue 3

Editorial: The Increasing Use of Genetically-altered Animals Threatens the Credibility of Directive 2010/63/EU

Michael Balls

The new EU Directive and the equivalent legislation in the EU Member States will be of little value, unless they can bring the production and use of genetically-altered animals under control and lead to a progressive and sustained reduction in laboratory animal use
You need to register (for free) to download this article. Please log in/register here.
2017-01-09T06:38:53+00:00 Tags: |

News & Views

ATLA staff writer

Honorary Life President of FRAME
Funding Opportunity for Disease Model Reviews
Drosophila Traumatic Brain Injury
In Vitro Model of Vocal Fold Mucosa
In Vitro Model of Adipose Tissue
Model of Satellite Cell Reactivation
Stem Cell-derived Hepatocyte Models for Toxicity Testing
In Vitro Bone Model
Carcinogenicity Test with Hepatocytes
You need to register (for free) to download this article. Please log in/register here.
2017-01-09T06:38:53+00:00 Tags: |

Comparative Studies of Apoptosis in Xenopus laevis and Mouse Thymoma Cell Lines

Rachel O. Johnson, Thomas V. Tittle, Maria P.M. Sefchick, Leslie D. Zettergren, Laurens N. Ruben, Richard H. Clothier and Michael Balls

With the use of in vitro methods and cell lines, functional aspects of apoptosis in the Xenopus laevis B3/B7 and mouse EL4 thymoma cell lines are revealed. Moreover, by using information gleaned from digital imaging and immunocytochemistry, changes in locations of key proteins implicated in apoptotic anti-cancer responses, e.g. p53 and Mdm2, are shown. Suggestions are offered as to what these results might mean with respect to the evolutionary conservation of the function and structure of these two molecules and to cancer resistance in amphibians. Finally, studies are described on resveratrol as an anti-cancer therapeutic reagent in the two thymoma cell lines and in normal X. laevis thymocytes.

This article is currently only available in full to paid subscribers. Click here to subscribe, or you will need to log in/register to buy and download this article

CAAT News & Views

ATLA staff writer

2014 CAAT Science-based Refinement Awards: Call for Proposals
In Vitro Medical Device Testing Symposium
Scientific Roadmap for the Future of Animal-free Systemic Toxicity Testing
Marcel Leist Receives Felix Wankel Animal Welfare Award
Mapping the Human Toxome: Human Toxome Project Website Launched
Recent CAAT Publications
You need to register (for free) to download this article. Please log in/register here.
2017-01-09T06:38:54+00:00 Tags: |

Fish as Research Tools: Alternatives to In Vivo Experiments

Marlien Schaeck, Wim Van den Broeck, Katleen Hermans and Annemie Decostere

The use of fish in scientific research is increasing worldwide, due to both the rapid expansion of the fish farming industry and growing awareness of questions concerning the humane use of mammalian models in basic research and chemical testing. As fish are lower on the evolutionary scale than mammals, they are considered to be less sentient. Fish models are providing researchers, and those concerned with animal welfare, with opportunities for adhering to the Three Rs principles of refinement, reduction and replacement. However, it should be kept in mind that fish should also be covered by the principles of the Three Rs. Indeed, various studies have shown that fish are capable of nociception, and of experiencing pain in a manner analogous to that in mammals. Thus, emphasis needs to be placed on the development of alternatives that replace, as much as possible, the use of all living vertebrate animals, including fish. This review gives the first comprehensive and critical overview of the existing alternatives for live fish experimental studies. The alternative methods described range from cell and tissue cultures, organ and perfusion models, and embryonic models, to in silico computer and mathematical models. This article aspires to guide scientists in the adoption of the correct alternative methods in their research, and, whenever possible, to reduce the use of live fish.

This article is currently only available in full to paid subscribers. Click here to subscribe, or you will need to log in/register to buy and download this article

Resistance to Cancer in Amphibians: A Role for Apoptosis?

Laurens N. Ruben, Rachel O. Johnson, Richard H. Clothier and Michael Balls

The rarity of spontaneous cancer in amphibians, and the difficulty of inducing cancer in these lower vertebrates, suggest that they possess an effective system for resistance to the development of cancer. The first part of this narrative presents evidence for cancer resistance in amphibians, and then a variety of studies designed to help understand the physiological basis for this resistance are reviewed. Here, our emphasis is on evidence with regard to the role that apoptosis might play.

This article is currently only available in full to paid subscribers. Click here to subscribe, or you will need to log in/register to buy and download this article

2017-01-09T06:38:54+00:00 Tags: , , |

Is Phenylbutazone a Genotoxic Carcinogen? A Weight-of-Evidence Assessment

Robert D. Combes

Published in silico, in vitro, in vivo laboratory animal and human data, together with information on biotransformation and data from structure–activity analyses with two decision-tree systems (ACToR and Toxtree), have been used in a weight-of-evidence (WoE) assessment to determine whether phenylbutazone (PBZ) is a genotoxic or a non-genotoxic carcinogen. This was undertaken to facilitate the risk assessment of human exposure to this veterinary drug via the consumption of horsemeat from treated animals. Despite problems with data interpretation at all tiers of the database, it was concluded that PBZ behaves like a genotoxic carcinogen with a threshold dose. This conclusion is based mainly on the results of a definitive rodent bioassay, and on the following observations: a) that PBZ has weak in vitro activity only at high concentrations in some genotoxicity assays, accompanied by high levels of cytotoxicity; b) that it (and a major metabolite) is able to cause sister chromatid exchanges in vivo in rodents; and c) that it can induce cytogenetic effects in vivo in humans. It also takes into account the known and predicted activities of the parent drug, some of its metabolites and two structural analogues, and, importantly, several of the drug’s other biochemical effects that are unrelated to toxicity. However, this conclusion is not fully supported by all the evidence, and much of the information is based on old papers. Therefore, more studies are required to establish whether the concentration thresholds seen in vitro would translate to dose thresholds for carcinogenicity, such that a safe dose-level could be defined for the purposes of assessing risk. It was disappointing that a WoE approach to evaluating all of the available hazard data, as is increasingly being advocated to improve the hazard identification paradigm, was unable to provide definitive answers in this case, particularly in view of the large numbers of animals that had been used to provide much of the information.

This article is currently only available in full to paid subscribers. Click here to subscribe, or you will need to log in/register to buy and download this article