Evaluation of Potential DNA-Damaging Effects of Nitenpyram and Imidacloprid in Human U937-Cells Using a New Statistical Approach to Analyse Comet Data

Abstract 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 μM, 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 μM, 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.

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Correction to: Evaluation of Potential DNA-Damaging Effects of Nitenpyram and Imidacloprid in Human U937-Cells Using a New Statistical Approach to Analyse Comet Data

Exposure and Health ◽

10.1007/s12403-021-00383-y ◽

2021 ◽

Author(s):

Erik Bivehed ◽

Anton Gustafsson ◽

Anders Berglund ◽

Björn Hellman

Keyword(s):

Statistical Approach ◽

U937 Cells ◽

Damaging Effects

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Quality control in oocytes by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level

eLife ◽

10.7554/elife.13909 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 29

Author(s):

Daniel Coutandin ◽

Christian Osterburg ◽

Ratnesh Kumar Srivastav ◽

Manuela Sumyk ◽

Sebastian Kehrloesser ◽

...

Keyword(s):

Dna Damage ◽

Quality Control ◽

Cellular Level ◽

Activation Mechanism ◽

Control Factor ◽

Dna Double Strand Breaks ◽

High Concentration ◽

P53 Family ◽

Strand Breaks ◽

Induced Apoptosis

Mammalian oocytes are arrested in the dictyate stage of meiotic prophase I for long periods of time, during which the high concentration of the p53 family member TAp63α sensitizes them to DNA damage-induced apoptosis. TAp63α is kept in an inactive and exclusively dimeric state but undergoes rapid phosphorylation-induced tetramerization and concomitant activation upon detection of DNA damage. Here we show that the TAp63α dimer is a kinetically trapped state. Activation follows a spring-loaded mechanism not requiring further translation of other cellular factors in oocytes and is associated with unfolding of the inhibitory structure that blocks the tetramerization interface. Using a combination of biophysical methods as well as cell and ovary culture experiments we explain how TAp63α is kept inactive in the absence of DNA damage but causes rapid oocyte elimination in response to a few DNA double strand breaks thereby acting as the key quality control factor in maternal reproduction.

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Role of Phytochemicals in Cancer Prevention

International Journal of Molecular Sciences ◽

10.3390/ijms20204981 ◽

2019 ◽

Vol 20 (20) ◽

pp. 4981 ◽

Cited By ~ 22

Author(s):

Alok Ranjan ◽

Sharavan Ramachandran ◽

Nehal Gupta ◽

Itishree Kaushik ◽

Stephen Wright ◽

...

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Cancer Chemoprevention ◽

Breast Cancer Patients ◽

Chemopreventive Agents ◽

Continuous Increase ◽

Natural Agents ◽

Anticancer Effects ◽

Alternative Approach ◽

High Risk Populations

The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.

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Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: A review

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2004.11.006 ◽

2005 ◽

Vol 206 (1) ◽

pp. 73-93 ◽

Cited By ~ 564

Author(s):

Weiling Xue ◽

David Warshawsky

Keyword(s):

Dna Damage ◽

Aromatic Hydrocarbons ◽

Metabolic Activation

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Incorporation of metabolic activation potentiates cyclophosphamide-induced DNA damage response in isogenic DT40 mutant cells

Mutagenesis ◽

10.1093/mutage/gev042 ◽

2015 ◽

Vol 30 (6) ◽

pp. 821-828

Author(s):

Kiyohiro Hashimoto ◽

Shunichi Takeda ◽

James A. Swenberg ◽

Jun Nakamura

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

Metabolic Activation ◽

Damage Response ◽

Mutant Cells

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The Effects of Perfluorooctane Sulfonate (PFOS) on Proliferation of Mouse Leydig Cells In Vitro

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.726-731.824 ◽

2013 ◽

Vol 726-731 ◽

pp. 824-828

Author(s):

De Yong Zhang ◽

Xiao Lu Xu ◽

Xiu Ying Shen ◽

Li Wang ◽

Yin Lu ◽

...

Keyword(s):

Dna Damage ◽

Leydig Cells ◽

Reproductive Toxicity ◽

Cellular Level ◽

Adherent Cells ◽

Healthy Mouse ◽

Damage Level ◽

Scge Assay ◽

Testis Tissue

To evaluate the male reproductive toxicity of PFOS on mammal animals at cellular level, mouse leydig cells were isolated from healthy mouse testis tissue and cultured in vitro. Adherent cells were treated with a serial concentration of PFOS for 4 more days of culture. Proliferation and DNA damage of the cells were analyzed by CCK assay and SCGE assay respectively. Forty-eight hours of treating with PFOS≧25μg/mL all inhibited the proliferation of the cells (p<0.05). PFOS seemed not to change the time for the cells to reach platform phase. DNA damage was also observed in the groups treated with PFOS dependent on dose and exposure time. The highest DNA damage level was averagely 17 cells per well in 96-well plates, which occurred to 62.5μg/mL group at 72h.

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Assessment of oxidative DNA damage and repair at single cellular level via real-time monitoring of 8-OHdG biomarker

Biosensors and Bioelectronics ◽

10.1016/j.bios.2010.08.029 ◽

2010 ◽

Vol 26 (4) ◽

pp. 1743-1749 ◽

Cited By ~ 40

Author(s):

Shradha Prabhulkar ◽

Chen-Zhong Li

Keyword(s):

Dna Damage ◽

Real Time ◽

Oxidative Dna Damage ◽

Cellular Level ◽

Real Time Monitoring ◽

Dna Damage And Repair

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MEC3, MEC1, and DDC2Are Essential Components of a Telomere Checkpoint Pathway Required for Cell Cycle Arrest during Senescence in Saccharomyces cerevisiae

Molecular Biology of the Cell ◽

10.1091/mbc.02-02-0012 ◽

2002 ◽

Vol 13 (8) ◽

pp. 2626-2638 ◽

Cited By ~ 81

Author(s):

Shinichiro Enomoto ◽

Lynn Glowczewski ◽

Judith Berman

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Dna Damage ◽

Telomerase Activity ◽

Cellular Level ◽

Dna Damage Checkpoint ◽

Average Growth ◽

Progressive Decline ◽

Checkpoint Response ◽

Essential Components

When telomerase is absent and/or telomeres become critically short, cells undergo a progressive decline in viability termed senescence. The telomere checkpoint model predicts that cells will respond to a damaged or critically short telomere by transiently arresting and activating repair of the telomere. We examined the senescence of telomerase-deficient Saccharomyces cerevisiae at the cellular level to ask if the loss of telomerase activity triggers a checkpoint response. As telomerase-deficient mutants were serially subcultured, cells exhibited a progressive decline in average growth rate and an increase in the number of cells delayed in the G2/M stage of the cell cycle. MEC3, MEC1, andDDC2, genes important for the DNA damage checkpoint response, were required for the cell cycle delay in telomerase-deficient cells. In contrast, TEL1,RAD9, and RAD53, genes also required for the DNA damage checkpoint response, were not required for the G2/M delay in telomerase-deficient cells. We propose that the telomere checkpoint is distinct from the DNA damage checkpoint and requires a specific set of gene products to delay the cell cycle and presumably to activate telomerase and/or other telomere repair activities.

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