Biomarkers as Predictive Tools in Toxicity Testing

Benford, Diane; Hanley, A. Bryan; Bottrill, Krys; Oehlschlager, Sarah; Balls, Michael; Branca, Francesco; Castegnaro, Jean Jaques; Descotes, J.; Hemminiki, Kari; Lindsay, David; Schilter, Benoı̂t

doi:10.1177/026119290002800104

Cited by 99 publications

(42 citation statements)

References 13 publications

(9 reference statements)

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“…During the past decade, issues of animal use and care in toxicology research and testing have become fundamental concerns for scientists not only for ethical reasons but also because of the difficulty in interpreting data owing to interspecies variation and exorbitant cost (Benford et al, 2000). This has led researchers to encourage the use of alternative organisms in toxicology.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, use of Drosophila falls within the recommendations of the European Center for the Validation of Alternative Methods (EC-VAM) (Festing et al, 1998), whose goal is to promote the scientific and regulatory acceptance of alternative methods that are of importance in the field of bioscience and that reduce, refine, or replace the use of laboratory animals (Benford et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Comparative toxic potential of market formulation of two organophosphate pesticides in transgenic Drosophila melanogaster (hsp70-lacZ)

et al. 2005

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This study investigated the working hypothesis that two widely used organophosphate pesticides; Nuvan and Dimecron, exert toxic effects in Drosophila. Transgenic D. melanogaster (hsp70-lacZ) was used as a model for assaying stress gene expression and AchE activity as an endpoint for toxicity and also to evaluate whether stress gene expression is sufficient to protect against toxic insult of the chemicals and to prevent tissue damage. The study was extended to investigate the effect of the pesticides on the life cycle and reproduction of the organism. The study showed that Nuvan affected emergence of the exposed flies more drastically than Dimecron and the effect was lethal at the highest tested concentration (0.075 ppm). While Nuvan at 0.0075 and 0.015 ppm concentrations affected reproduction of the flies significantly, the effect of Dimecron was significant only at 0.015 and 0.075 ppm. Nuvan-exposed third-instar larvae exhibited a 1.2-fold to 1.5-fold greater hsp70 expression compared to Dimecron at concentrations ranging from 0.0075 to 0.075 ppm following 12 and 18 h exposure. While maximum expression of hsp70 was observed in Nuvan-exposed third-instar larval tissues following 18 h exposure at 0.075 ppm, Dimecron at the same dietary concentration induced a maximum expression of hsp70 following 24 h exposure. Further, concomitant with a significant induction of hsp70, significant inhibition of AchE was observed following chemical exposure and temperature shock. Concurrent with a significant decline in hsp70 expression in Nuvan-exposed larvae after 48 h at 0.075 ppm, tissue damage was evident. Dimecron-exposed larvae exhibited a plateau in hsp70 induction even after 48 h exposure and moderate tissue damage was observed in these larvae. The present study suggests that Nuvan is more cytotoxic than Dimecron in transgenic Drosophila melanogaster.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative toxic potential of market formulation of two organophosphate pesticides in transgenic Drosophila melanogaster (hsp70-lacZ)

et al. 2005

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“…[33][34][35][36][37][38] Concerns have been raised about the ethics and use of animals for toxicology research and testing, and emphasis now is given to the use of alternatives to mammals in research as well as education. The European Centre for the Validation of Alternative Methods (ECVAM) promotes scientific and regulatory acceptance of alternative methods for reducing, refining or replacing the use of laboratory animals 39,40 and recommends D. melanogaster as an alternative to animal models for testing and research.…”

Section: The Alkaline Comet Assay In Drosophila Melanogastermentioning

confidence: 99%

Detection of DNA Damage in Drosophila and Mouse

Dhawan

Bajpayee

Parmar

2009

The Comet Assay in Toxicology

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The single-cell gel electrophoresis (SCGE)/Comet assay has, since its inception, been widely used for the simple, sensitive and rapid determination of DNA damage and repair, quantitatively as well as qualitatively in individual cell populations. 1 Comet is the perfect acronym for credible observation and measurement of exposure to toxicants. The assay combines the simplicity of biochemical techniques for detecting DNA single-strand breaks with the single-cell approach of cytogenetic assays. The advantages of the assay include its need for small numbers of cells per sample (o10 000), collection of data at the level of the individual cell, allowing for robust statistical analyses, its sensitivity for detecting quantitative and qualitative DNA damage. The assay has versatility in detecting DNA single-and double-strand breaks, oxidative DNA damage, crosslinks as well as apoptosis and necrosis in proliferating or nonproliferating cells, and has thus gained popularity as a test for genetic toxicology. Single cells obtained from various organisms ranging from simple bacteria (prokaryotes) to complex humans (eukaryotes) have been used to monitor in vitro or in vivo genotoxicity of chemicals. 2 It has also been used Issues in Toxicology No 5

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“…The high sensitivity to toxic substances makes D. melanogaster an excellent bioindicator in the detection of environmental pollutants, which is why it is used as a replacement of vertebrate species in toxicity assay [15]. …”

Section: Introductionmentioning

confidence: 99%

Surface Water Impacted by Rural Activities Induces Genetic Toxicity Related to Recombinagenic Events in Vivo

Neto

Carli

Kotzal

et al. 2016

IJERPH

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This investigation assessed the interaction of surface water samples with DNA to quantitatively and qualitatively characterize their mutagenic and/or recombinagenic activity. Samples were obtained at three different sites along the Tocantins River (Tocantins State, Brazil). The area has withstood the impact mainly of rural activities, which release different chemical compounds in the environment. The Drosophila melanogaster Somatic Mutation and Recombination Test (SMART) was performed in standard (ST) and high bioactivation (HB) crosses. SMART is useful for the detection of mutational and recombinational events induced by genotoxins of direct and indirect action. Results demonstrated that samples collected in both seasons were able to induce increments on the mutant spot frequencies in the larvae of the HB cross. Genotoxicity was related to a massive recombinagenic activity. The positive responses ascribed to only the HB cross means that it is linked to pro-genotoxins requiring metabolic activation. The SMART wing test in Drosophila melanogaster was shown to be highly sensitive to detect genotoxic agents present in the aquatic environment impacted by agriculture.

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Biomarkers as Predictive Tools in Toxicity Testing

Cited by 99 publications

References 13 publications

Comparative toxic potential of market formulation of two organophosphate pesticides in transgenic Drosophila melanogaster (hsp70-lacZ)

Comparative toxic potential of market formulation of two organophosphate pesticides in transgenic Drosophila melanogaster (hsp70-lacZ)

Detection of DNA Damage in Drosophila and Mouse

Surface Water Impacted by Rural Activities Induces Genetic Toxicity Related to Recombinagenic Events in Vivo

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