Dissociation of DNA damage and mitochondrial injury caused by hydrogen peroxide in SV-40 transformed lung epithelial cells

Fujii, Yukihiko; Tomita, Katsuyuki; Sano, Hiroyuki; Yamasaki, Akira; Hitsuda, Yutaka; Adcock, Ian M.; Shimizu, Eiji

doi:10.1186/1475-2867-2-16

Cited by 9 publications

(2 citation statements)

References 44 publications

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“…Mitochondrial activity was stimulated by H 2 O 2 alone and in combination with NO 2− at the nspDBD conditions in comparison to the untreated control, as shown inFigure 6b,e. H 2 O 2 is a potent oxidizer and is well known to induce mitochondrial stress at concentrations as low as 100 µM[50]. NO 2 − alone had no discernable effect on mitochondrial O 2 − production for either of the mock treatments.…”

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confidence: 95%

GSH Modification as a Marker for Plasma Source and Biological Response Comparison to Plasma Treatment

et al. 2020

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This study investigated the use of glutathione as a marker to establish a correlation between plasma parameters and the resultant liquid chemistry from two distinct sources to predefined biological outcomes. Two different plasma sources were operated at parameters that resulted in similar biological responses: cell viability, mitochondrial activity, and the cell surface display of calreticulin. Specific glutathione modifications appeared to be associated with biological responses elicited by plasma. These modifications were more pronounced with increased treatment time for the European Cooperation in Science and Technology Reference Microplasma Jet (COST-Jet) and increased frequency for the dielectric barrier discharge and were correlated with more potent biological responses. No correlations were found when cells or glutathione were exposed to exogenously added long-lived species alone. This implied that short-lived species and other plasma components were required for the induction of cellular responses, as well as glutathione modifications. These results showed that comparisons of medical plasma sources could not rely on measurements of long-lived chemical species; rather, modifications of biomolecules (such as glutathione) might be better predictors of cellular responses to plasma exposure.

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confidence: 95%

GSH Modification as a Marker for Plasma Source and Biological Response Comparison to Plasma Treatment

et al. 2020

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“…It is possible that C6 glioma cells have inherent protection mechanisms from ROS-induced DNA damage aside from neutralizing ROS such as enhanced DNA repair processes. Previous studies in alveolar epithelium have demonstrated resistance to DNA damage in spite of chronically elevated H 2 O 2 concentrations 52 . Further studies are warranted on the unique nature of C6 cells to further understand their resistance to pFUS-induced DNA damage.…”

Section: Discussionmentioning

confidence: 96%

Cytosolic Ca²⁺ transients during pulsed focused ultrasound generate reactive oxygen species and cause DNA damage in tumor cells

Rosenblatt¹,

Frank²,

Burks³

2021

Theranostics

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Mechanical forces from non-ablative pulsed focused ultrasound (pFUS) generate pro-inflammatory tumor microenvironments (TME), marked by increased cytokines, chemokines, and trophic factors, as well as immune cell infiltration and reduced tumor growth. pFUS also causes DNA damage within tumors, which is a potent activator of immunity and could contribute to changes in the TME. This study investigated mechanisms behind the mechanotransductive effects of pFUS causing DNA damage in several tumor cell types. Methods: 4T1 (murine breast tumor), B16 (murine melanoma), C6 (rat glioma), or MDA-MB-231 (human breast tumor) cells were sonicated in vitro (1.1MHz; 6MPa PNP; 10ms pulses; 10% duty cycle; 300 pulses). DNA damage was detected by TUNEL, apoptosis was measured by immunocytochemistry for cleaved caspase-3. Calcium, superoxide, and H 2 O 2 were detected by fluorescent indicators and modulated by BAPTA-AM, mtTEMPOL, or Trolox, respectively. Results: pFUS increased TUNEL reactivity (range = 1.6-2.7-fold) in all cell types except C6 and did not induce apoptosis in any cell line. All lines displayed cytosolic Ca 2+ transients during sonication. pFUS increased superoxide (range = 1.6-2.0-fold) and H 2 O 2 (range = 2.3-2.8-fold) in all cell types except C6. BAPTA-AM blocked increased TUNEL reactivity, superoxide and H 2 O 2 formation, while Trolox also blocked increased TUNEL reactivity increased after pFUS. mtTEMPOL allowed H 2 O 2 formation and did not block increased TUNEL reactivity after pFUS. Unsonicated C6 cells had higher baseline concentrations of cytosolic Ca 2+ , superoxide, and H 2 O 2 , which were not associated with greater baseline TUNEL reactivity than the other cell lines. Conclusions: Mechanotransduction of pFUS directly induces DNA damage in tumor cells by cytosolic Ca 2+ transients causing formation of superoxide and subsequently, H 2 O 2 . These results further suggest potential clinical utility for pFUS. However, the lack of pFUS-induced DNA damage in C6 cells demonstrates a range of potential tumor responses that may arise from physiological differences such as Ca 2+ or redox homeostasis.

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Susceptibility of lung epithelial cells to alkylating genotoxic insult

Nagy

Ádány

Szűcs

et al. 2013

Environ and Mol Mutagen

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Alkylation is one of the most common types of DNA damage that can lead to mutations and cancer. Lung is the primary target organ of airborne alkylators such as ethylene oxide (EO). However, the ability of EO to cause lung cancer has not been clearly demonstrated yet. The aim of this study was to investigate the susceptibility of lung cells to alkylating DNA insult by detecting EO-mediated DNA damage with the alkaline comet assay in human lung epithelial cells, peripheral blood lymphocytes, and keratinocytes. The susceptibility of these cell types toward the alkylating insult induced by EO was compared against the oxidative DNA insult induced by hydrogen peroxide (H2 O2 ). Due to the volatility of EO, its active concentrations were monitored by gas chromatography during exposure and were found to decrease significantly in a time-dependent manner. EO induced a statistically significant genotoxic effect at the lowest concentration used (16.4 µM) in lung epithelial cells and in lymphocytes, while in keratinocytes, a genotoxic effect was not detected until 55.5 µM EO. However, lung epithelial cells demonstrated increased resistance to oxidative insult. In fact, oxidative DNA damage detectable by endonuclease treatment was minimal in lung cells compared with the other cell types. These results suggest an increased sensitivity of lung epithelial cells toward the alkylating effects of EO, which was not observed for oxidative DNA damage. Our findings point out the importance of DNA alkylation and the possible role of EO on the induction of lung cancer.

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Dissociation of DNA damage and mitochondrial injury caused by hydrogen peroxide in SV-40 transformed lung epithelial cells

Cited by 9 publications

References 44 publications

GSH Modification as a Marker for Plasma Source and Biological Response Comparison to Plasma Treatment

GSH Modification as a Marker for Plasma Source and Biological Response Comparison to Plasma Treatment

Cytosolic Ca²⁺ transients during pulsed focused ultrasound generate reactive oxygen species and cause DNA damage in tumor cells

Susceptibility of lung epithelial cells to alkylating genotoxic insult

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Dissociation of DNA damage and mitochondrial injury caused by hydrogen peroxide in SV-40 transformed lung epithelial cells

Cited by 9 publications

References 44 publications

GSH Modification as a Marker for Plasma Source and Biological Response Comparison to Plasma Treatment

GSH Modification as a Marker for Plasma Source and Biological Response Comparison to Plasma Treatment

Cytosolic Ca2+ transients during pulsed focused ultrasound generate reactive oxygen species and cause DNA damage in tumor cells

Susceptibility of lung epithelial cells to alkylating genotoxic insult

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Cytosolic Ca²⁺ transients during pulsed focused ultrasound generate reactive oxygen species and cause DNA damage in tumor cells