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Evaluation of Potential DNA-Damaging Effects of Nitenpyram and Imidacloprid in Human U937-Cells Using a New Statistical Approach to Analyse Comet Data
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.ORCID iD: 0000-0003-2471-1432
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Statstikakademin AB, S-75321 Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2019 (English)In: EXPOSURE AND HEALTH, ISSN 2451-9766Article in journal (Refereed) Epub ahead of print
Abstract [en]

Even if the two neonicotinoids nitenpyram and imidacloprid have been considered safe for humans, their potential genotoxicity still remains a matter of discussion. The DNA-damaging effects of these two compounds were therefore evaluated in a lymphoma cell line of human origin (U-937) using the comet assay after 3-h exposure to up to 50 mu M, with or without metabolic activation using S9 from human liver. The comet data were analysed using a traditional one-way ANOVA after pooling the data on cellular level, and a new alternative approach we have called Uppsala Comet Data Analysis Strategy (UCDAS). UCDAS is a proportional odds model tailored to continuous outcomes, taking the number of pooled cultures, slides and cells into consideration in the same analysis. To the best of our knowledge, the UCDAS approach when analysing comet data has never been presented before. Without metabolic activation, no increase in DNA damage was observed in the neonicotinoide-exposed cells. Nitenpyram was also without DNA-damaging effects when S9 was added. However, in the presence of S9, imidacloprid was found to increase the level of DNA damage. Whereas the ANOVA showed an increase (P<0.001) both at 5 and 50 mu M, UCDAS showed an increase only at the lowest concentration (P<0.001). Based on these findings, the two neonicotinoids seem to be of little concern when it comes to their potential genotoxicity. However, since the U-937 cells were rather resistant to our positive controls, they may not be the best cells to use when evaluating potential genotoxicity of chemicals.

Place, publisher, year, edition, pages
2019.
Keywords [en]
Neonicotinoids, Imidacloprid, Nitenpyram, In vitro comet assay, DNA damage, Metabolic bioactivation, Statistical analysis of comet data
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-397667DOI: 10.1007/s12403-019-00328-6ISI: 000493365500001OAI: oai:DiVA.org:uu-397667DiVA, id: diva2:1374003
Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved

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Bivehed, ErikHellman, Björn

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