Validation of the γH2AX biomarker for genotoxicity assessment: a review

Kopp, Benjamin T.; Khoury, Laure; Audebert, Marc

doi:10.1007/s00204-019-02511-9

Cited by 170 publications

(104 citation statements)

References 89 publications

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“…Although forskolin modestly decreased PRL levels (P ≤ 0.05 vs. vehicle) ( Figure 5C), neither forskolin alone nor the combination of forskolin and rolipram altered FSH levels ( Figure 5D). Phosphorylated H2AX (γH2AX) is considered an early sensitive biomarker for genotoxicity and for monitoring DNA damage (31). Histone H2AX is phosphorylated early upon DNA damage, enabling the accumulation of DNA damage response proteins, and activates cell-cycle checkpoint pathways including p53/p21 Wif1/Cip1 .…”

Section: Resultsmentioning

confidence: 99%

DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas

Ben-Shlomo¹,

Deng²,

Ding³

et al. 2020

Journal of Clinical Investigation

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Section: Resultsmentioning

confidence: 99%

DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas

Ben-Shlomo¹,

Deng²,

Ding³

et al. 2020

Journal of Clinical Investigation

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“…Whether for tumor HCT-116 cells or for normal dermal fibroblasts, cisplatin and bleomycin were genotoxic as revealed by induction of the phosphorylation of histone H2AX, a biomarker of global DNA damage [18]. As shown in Figure 2, compared to the control, a significant increase in genotoxicity appeared above 10 µ M for cisplatin alone and 50 nM for bleomycin alone in a concentration-dependent manner of the antitumor drugs cisplatin (1, 10, 50, 100 µ M) and bleomycin (5, 50, 500, 1000 nM).…”

Section: Electrochemotherapy Potentiates Genotoxic and Cytotoxic Effementioning

confidence: 99%

Calcium Delivery by Electroporation Induces In Vitro Cell Death through Mitochondrial Dysfunction without DNA Damages

Gibot

Montigny

Baaziz

et al. 2020

Cancers

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Adolescent cancer survivors present increased risks of developing secondary malignancies due to cancer therapy. Electrochemotherapy is a promising anti-cancer approach that potentiates the cytotoxic effect of drugs by application of external electric field pulses. Clinicians proposed to associate electroporation and calcium. The current study aims to unravel the toxic mechanisms of calcium electroporation, in particular if calcium presents a genotoxic profile and if its cytotoxicity comes from the ion itself or from osmotic stress. Human dermal fibroblasts and colorectal HCT-116 cell line were treated by electrochemotherapy using bleomycin, cisplatin, calcium, or magnesium. Genotoxicity, cytotoxicity, mitochondrial membrane potential, ATP content, and caspases activities were assessed in cells grown on monolayers and tumor growth was assayed in tumor spheroids. Results in monolayers show that unlike cisplatin and bleomycin, calcium electroporation induces cell death without genotoxicity induction. Its cytotoxicity correlates with a dramatic fall in mitochondrial membrane potential and ATP depletion. Opposite of magnesium, over seven days of calcium electroporation led to spheroid tumor growth regression. As non-genotoxic, calcium has a better safety profile than conventional anticancer drugs. Calcium is already authorized by different health authorities worldwide. Therefore, calcium electroporation should be a cancer treatment of choice due to the reduced potential of secondary malignancies.

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“…γ-H2AX is the phosphorylated form of the histone H2AX, which becomes phosphorylated on serine residue 139 in response to DNA DSB induction and forms nuclear foci adjacent to the sites of the DSBs [58]. Because the phosphorylation of H2AX is rapid, abundant, and correlates well with the number of DSBs [59], it is a very sensitive marker for DNA DSB induction (for a review see: [60]).…”

Section: Induction Of Dna Double-strand Breaks By Cyn Bps and Theirmentioning

confidence: 99%

Plastics in Cyanobacterial Blooms—Genotoxic Effects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells

Hercog

Štern

Maisanaba

et al. 2020

Toxins

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Ever-expanding environmental pollution is causing a rise in cyanobacterial blooms and the accumulation of plastics in water bodies. Consequently, exposure to mixtures of cyanotoxins and plastic-related contaminants such as bisphenols (BPs) is of increasing concern. The present study describes genotoxic effects induced by co-exposure to one of the emerging cyanotoxins—cylindrospermopsin (CYN)—(0.5 µg/mL) and BPs (bisphenol A (BPA), S (BPS), and F (BPF); (10 µg/mL)) in HepG2 cells after 24 and 72 h of exposure. The cytotoxicity was evaluated with an MTS assay and genotoxicity was assessed through the measurement of the induction of DNA double strand breaks (DSB) with the γH2AX assay. The deregulation of selected genes (xenobiotic metabolic enzyme genes, DNA damage, and oxidative response genes) was assessed using qPCR. The results showed a moderate reduction of cell viability and induction of DSBs after 72 h of exposure to the CYN/BPs mixtures and CYN alone. None of the BPs alone reduced cell viability or induced DSBs. No significant difference was observed between CYN and CYN/BPs exposed cells, except with CYN/BPA, where the antagonistic activity of BPA against CYN was indicated. The deregulation of some of the tested genes (CYP1A1, CDKN1A, GADD45A, and GCLC) was more pronounced after exposure to the CYN/BPs mixtures compared to single compounds, suggesting additive or synergistic action. The present study confirms the importance of co-exposure studies, as our results show pollutant mixtures to induce effects different from those confirmed for single compounds.

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Validation of the γH2AX biomarker for genotoxicity assessment: a review

Cited by 170 publications

References 89 publications

DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas

DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas

Calcium Delivery by Electroporation Induces In Vitro Cell Death through Mitochondrial Dysfunction without DNA Damages

Plastics in Cyanobacterial Blooms—Genotoxic Effects of Binary Mixtures of Cylindrospermopsin and Bisphenols in HepG2 Cells

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