In vitro investigations of glycidamide-induced DNA lesions in mouse male germ cells and in mouse and human lymphocytes

Hansen, Siri Helland; Olsen, Ann‐Karin; Søderlund, Erik J.; Brunborg, Gunnar

doi:10.1016/j.mrgentox.2009.12.012

Cited by 49 publications

(39 citation statements)

References 69 publications

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“…The increased level of oxidative DNA lesions to 20% TI with Fpg in Ogg1 −/− mice is in agreement with previous experiments in our laboratory [25] and was independent of the treatment (BaP or corn oil). The median % TI data was slightly higher in Ogg1 −/− mice treated with BaP compared to Ogg1 −/− mice treated with corn oil (23.08% TI and 18.93% TI), but this difference was not statistically significant (Table I).…”

Section: Resultssupporting

confidence: 93%

“…The alkaline SCGE may lead to false negative results when an agent gives rise to bulky DNA lesions or alkali-stabile base modifications as suggested in this study. Whereas the Pig-a assay is currently limited to blood cells, the SCGE assay is theoretically applicable in any tissue from which it is possible to isolate single cells or nuclei, including reproductive tissues such as testicle and enables thus direct assessment of potential germ cell mutagens [25, 35]. Therefore, experiments must be designed according to the assumed type(s) and tissue locations of chemicals’ genotoxic effects and interpreted with great care.…”

Section: Discussionmentioning

confidence: 99%

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Single cell gel electrophoresis (SCGE) and Pig-a mutation assay in vivo-tools for genotoxicity testing from a regulatory perspective: A study of benzo[a]pyrene in Ogg1−/− mice

Graupner

Instanes

Dertinger

et al. 2014

Mutation Research/Genetic Toxicology and Environmental Mutagene

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The OECD has developed test guidelines (TG) to identify agents with genotoxic effects. The in vivo alkaline single cell gel electrophoresis (SCGE) assay is currently being prepared to become such a TG. The performance of a combined SCGE/Pig-a gene mutation study was evaluated with the prototypical genotoxicant benzo[a]pyrene (BaP) at an exposure level known to induce germ cell mutation. We aimed to better understand (i) the strengths and weaknesses of the two methods applied in blood and their potential to predict germ cell mutagenicity, and (ii) the involvement of reactive oxygen species (ROS) following in vivo BaP-exposure. To explore the involvement of ROS on BaP genotoxicity, we utilized a mouse model deficient in a DNA glycosylase. Specifically, C57BL/6 mice (Ogg1+/+ and Ogg1−/−) were treated for three consecutive days with 50 mg BaP/kg/day. DNA damage in nucleated blood cells was measured four hours after the last treatment with the SCGE assay, with and without Formamidopyrimidine DNA glycosylase (Fpg). Pig-a mutant phenotype blood erythrocytes were analysed two and four weeks after treatment. BaP-induced DNA lesions were not significantly increased in either version of the SCGE assay. The phenotypic mutation frequencies for immature and mature erythrocytes were significantly increased after two weeks. These effects were not affected by genotype, suggesting oxidative damage may have a minor role in BaP genotoxicity, at least in the acute exposure situation studied here. While both assays are promising tools for risk assessment, these results highlight the necessity of understanding the limitations regarding each assay’s ability to detect chemicals’ genotoxic potential.

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Section: Resultssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Single cell gel electrophoresis (SCGE) and Pig-a mutation assay in vivo-tools for genotoxicity testing from a regulatory perspective: A study of benzo[a]pyrene in Ogg1−/− mice

Graupner

Instanes

Dertinger

et al. 2014

Mutation Research/Genetic Toxicology and Environmental Mutagene

Self Cite

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“…Zhang et al (2009) have established the efficacy of HT against oxidative DNA damage in Hep G2 cells after acrylamide treatment. The genotoxicity of ACR might be attributed to glycidamide, an epoxide metabolite produced by hepatic cytochrome P450 enzymes, especially P450 2E1 (Lamy et al 2008;Hansen et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Dietary unsaponifiable fraction of extra virgin olive oil supplementation attenuates lung injury and DNA damage of rats co-exposed to aluminum and acrylamide

Ghorbel

Chaâbane

Boudawara

et al. 2016

Environ Sci Pollut Res

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Aluminum chloride (AlCl3) and acrylamide (ACR) are well known as environmental pollutants inducing oxidative stress. Our study investigated the effects of these contaminants and if the hydrophilic fraction of extra virgin olive oil was able to prevent lung oxidative stress and DNA damage. Animals were divided into four groups of six each: group 1, serving as controls, received distilled water; group 2 received in drinking water aluminum chloride (50 mg/ kg body weight) and by gavage acrylamide (20 mg/kg body weight); group 3 received both aluminum and acrylamide in the same way and the same dose as group 2 and hydrophilic fraction from olive oil (OOHF) (1 ml) by gavage; group 4 received only OOHF by gavage. Exposure of rats to both aluminum and acrylamide provoked oxidative stress in lung tissue based on biochemical parameters and histopathological alterations. In fact, we have observed an increase in malondialdehyde (MDA), H2O2, and advanced oxidation protein product (AOPP) and a decrease in reduced glutathione (GSH), non-protein thiols (NPSH), and vitamin C levels. Activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were also decreased. Histopathological changes in lung tissue were noted like emphysema, vascular congestion, and infiltration of inflammatory cells. A random DNA degradation was observed on agarose gel in the lung of AlCl3 and acrylamide (ACR)-treated rats. Co-administration of OOHF to treated rats improved biochemical parameters to near control values and lung histoarchitecture. The smear formation of genomic DNA was reduced. The hydrophilic fraction of extra virgin olive oil might provide a basis for developing a new dietary supplementation strategy in order to prevent lung tissue damage.

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“…The experiments with the three chemicals, which all have documented genotoxic properties (Ribas et al, 1995(Ribas et al, , 1996González et al, 2005;Ateeq et al, 2005;Hansen et al, 2010;Juchimiuk et al, 2006), yielded full concentration-response curves (Figure 1), allowing for determination of isoeffective concentrations for the mixture genotoxicity experiment. As shown in Figure 2, CA seems to underestimate the mixture effects, especially at the low concentrations, indicating that the genotoxic mixture yielded synergistic effects at low concentrations.…”

Section: Discussionmentioning

confidence: 99%

Mixture Genotoxicity of 2,4-Dichlorophenoxyacetic Acid, Acrylamide, and Maleic Hydrazide on Human Caco-2 Cells Assessed with Comet Assay

Syberg

Binderup²,

Cedergreen

et al. 2015

Journal of Toxicology and Environmental Health, Part A

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Assessment of genotoxic properties of chemicals is mainly conducted only for single chemicals, without taking mixture genotoxic effects into consideration. The current study assessed mixture effects of the three known genotoxic chemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), acrylamide (AA), and maleic hydrazide (MH), in an experiment with a fixed ratio design setup. The genotoxic effects were assessed with the single-cell gel electrophoresis assay (comet assay) for both single chemicals and the ternary mixture. The concentration ranges used were 0-1.4, 0-20, and 0-37.7 mM for 2,4-D, AA, and MH, respectively. Mixture toxicity was tested with a fixed ratio design at a 10:23:77% ratio for 2.4-D:AA:MH. Results indicated that the three chemicals yielded a synergistic mixture effect. It is not clear which mechanisms are responsible for this interaction. A few possible interactions are discussed, but further investigations including in vivo studies are needed to clarify how important these more-than-additive effects are for risk assessment.

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In vitro investigations of glycidamide-induced DNA lesions in mouse male germ cells and in mouse and human lymphocytes

Cited by 49 publications

References 69 publications

Single cell gel electrophoresis (SCGE) and Pig-a mutation assay in vivo-tools for genotoxicity testing from a regulatory perspective: A study of benzo[a]pyrene in Ogg1−/− mice

Single cell gel electrophoresis (SCGE) and Pig-a mutation assay in vivo-tools for genotoxicity testing from a regulatory perspective: A study of benzo[a]pyrene in Ogg1−/− mice

Dietary unsaponifiable fraction of extra virgin olive oil supplementation attenuates lung injury and DNA damage of rats co-exposed to aluminum and acrylamide

Mixture Genotoxicity of 2,4-Dichlorophenoxyacetic Acid, Acrylamide, and Maleic Hydrazide on Human Caco-2 Cells Assessed with Comet Assay

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