Do cytotoxicity and cell death cause false positive results in the in vitro comet assay?

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Do cytotoxicity and cell death cause false positive results in the in vitro comet assay? / Azqueta, Amaya; Stopper, Helga; Zegura, Bojana; Dusinska, Maria; Moller, Peter.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 881, 503520, 2022.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Azqueta, A, Stopper, H, Zegura, B, Dusinska, M & Moller, P 2022, 'Do cytotoxicity and cell death cause false positive results in the in vitro comet assay?', Mutation Research - Genetic Toxicology and Environmental Mutagenesis, vol. 881, 503520. https://doi.org/10.1016/j.mrgentox.2022.503520

APA

Azqueta, A., Stopper, H., Zegura, B., Dusinska, M., & Moller, P. (2022). Do cytotoxicity and cell death cause false positive results in the in vitro comet assay? Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 881, [503520]. https://doi.org/10.1016/j.mrgentox.2022.503520

Vancouver

Azqueta A, Stopper H, Zegura B, Dusinska M, Moller P. Do cytotoxicity and cell death cause false positive results in the in vitro comet assay? Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2022;881. 503520. https://doi.org/10.1016/j.mrgentox.2022.503520

Author

Azqueta, Amaya ; Stopper, Helga ; Zegura, Bojana ; Dusinska, Maria ; Moller, Peter. / Do cytotoxicity and cell death cause false positive results in the in vitro comet assay?. In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2022 ; Vol. 881.

Bibtex

@article{afd81a37c29f4057b53c7fbc2539f935,
title = "Do cytotoxicity and cell death cause false positive results in the in vitro comet assay?",
abstract = "The comet assay is used to measure DNA damage induced by chemical and physical agents. High concentrations of test agents may cause cytotoxicity or cell death, which may give rise to false positive results in the comet assay. Systematic studies on genotoxins and cytotoxins (i.e. non-genotoxic poisons) have attempted to establish a threshold of cytotoxicity or cell death by which DNA damage results measured by the comet assay could be regarded as a false positive result. Thresholds of cytotoxicity/cell death range from 20% to 50% in various publications. Curiously, a survey of the latest literature on comet assay results from cell culture studies suggests that one-third of publications did not assess cytotoxicity or cell death. We recommend that it should be mandatory to include results from at least one type of assay on cytotoxicity, cell death or cell proliferation in publications on comet assay results. A combination of cytotoxicity (or cell death) and proliferation (or colony forming efficiency assay) is preferable in actively proliferating cells because it covers more mechanisms of action. Applying a general threshold of cytotoxicity/cell death to all types of agents may not be applicable; however, 25% compared to the concurrent negative control seems to be a good starting value to avoid false positive comet assay results. Further research is needed to establish a threshold value to distinguish between true and poten-tially false positive genotoxic effects detected by the comet assay.",
keywords = "Cometassay, DNAdamage, Cytotoxicity, Celldeath, Apoptosis, Viability, DNA-STRAND BREAKS, ENGINEERED NANOMATERIALS, INDUCED APOPTOSIS, HEPATOCYTE ASSAY, OXIDATIVE DAMAGE, TRYPAN BLUE, GENOTOXICITY, VIVO, VALIDATION, MECHANISMS",
author = "Amaya Azqueta and Helga Stopper and Bojana Zegura and Maria Dusinska and Peter Moller",
year = "2022",
doi = "10.1016/j.mrgentox.2022.503520",
language = "English",
volume = "881",
journal = "Mutation Research - Genetic Toxicology and Environmental Mutagenesis",
issn = "1383-5718",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Do cytotoxicity and cell death cause false positive results in the in vitro comet assay?

AU - Azqueta, Amaya

AU - Stopper, Helga

AU - Zegura, Bojana

AU - Dusinska, Maria

AU - Moller, Peter

PY - 2022

Y1 - 2022

N2 - The comet assay is used to measure DNA damage induced by chemical and physical agents. High concentrations of test agents may cause cytotoxicity or cell death, which may give rise to false positive results in the comet assay. Systematic studies on genotoxins and cytotoxins (i.e. non-genotoxic poisons) have attempted to establish a threshold of cytotoxicity or cell death by which DNA damage results measured by the comet assay could be regarded as a false positive result. Thresholds of cytotoxicity/cell death range from 20% to 50% in various publications. Curiously, a survey of the latest literature on comet assay results from cell culture studies suggests that one-third of publications did not assess cytotoxicity or cell death. We recommend that it should be mandatory to include results from at least one type of assay on cytotoxicity, cell death or cell proliferation in publications on comet assay results. A combination of cytotoxicity (or cell death) and proliferation (or colony forming efficiency assay) is preferable in actively proliferating cells because it covers more mechanisms of action. Applying a general threshold of cytotoxicity/cell death to all types of agents may not be applicable; however, 25% compared to the concurrent negative control seems to be a good starting value to avoid false positive comet assay results. Further research is needed to establish a threshold value to distinguish between true and poten-tially false positive genotoxic effects detected by the comet assay.

AB - The comet assay is used to measure DNA damage induced by chemical and physical agents. High concentrations of test agents may cause cytotoxicity or cell death, which may give rise to false positive results in the comet assay. Systematic studies on genotoxins and cytotoxins (i.e. non-genotoxic poisons) have attempted to establish a threshold of cytotoxicity or cell death by which DNA damage results measured by the comet assay could be regarded as a false positive result. Thresholds of cytotoxicity/cell death range from 20% to 50% in various publications. Curiously, a survey of the latest literature on comet assay results from cell culture studies suggests that one-third of publications did not assess cytotoxicity or cell death. We recommend that it should be mandatory to include results from at least one type of assay on cytotoxicity, cell death or cell proliferation in publications on comet assay results. A combination of cytotoxicity (or cell death) and proliferation (or colony forming efficiency assay) is preferable in actively proliferating cells because it covers more mechanisms of action. Applying a general threshold of cytotoxicity/cell death to all types of agents may not be applicable; however, 25% compared to the concurrent negative control seems to be a good starting value to avoid false positive comet assay results. Further research is needed to establish a threshold value to distinguish between true and poten-tially false positive genotoxic effects detected by the comet assay.

KW - Cometassay

KW - DNAdamage

KW - Cytotoxicity

KW - Celldeath

KW - Apoptosis

KW - Viability

KW - DNA-STRAND BREAKS

KW - ENGINEERED NANOMATERIALS

KW - INDUCED APOPTOSIS

KW - HEPATOCYTE ASSAY

KW - OXIDATIVE DAMAGE

KW - TRYPAN BLUE

KW - GENOTOXICITY

KW - VIVO

KW - VALIDATION

KW - MECHANISMS

U2 - 10.1016/j.mrgentox.2022.503520

DO - 10.1016/j.mrgentox.2022.503520

M3 - Journal article

VL - 881

JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

SN - 1383-5718

M1 - 503520

ER -

ID: 315455899