DNA damage by reactive species: Mechanisms, mutation and repair

Jena, N. R.

doi:10.1007/s12038-012-9218-2

Cited by 292 publications

(218 citation statements)

References 125 publications

Supporting

Mentioning

207

Contrasting

Unclassified

Order By: Relevance

“…ROS induced by compound 1 activate oxidative stress response pathways, which we propose are responsible for DNA damage. DNA is a well-known target for ROS, particularly guanine bases (45). Compound 1 is equipotent in Pt-resistant cancer cell lines, with ROS-centered DNA damage not repairable by enhancement of Pt-induced DDR (13).…”

Section: Discussionmentioning

confidence: 99%

Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells

Hearn

Romero‐Canelón

Munro

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The organometallic “half-sandwich” compound [Os(η6-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF6 is 49× more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH dehydrogenase) in the electron transport chain. ND5 is a proton pump, helping to maintain the coupling gradient in mitochondria. The identified mutations correspond to known protein variants (p.I257V, p.N447S, and p.L517P), not reported previously in epithelial ovarian cancer. Time-series RNA sequencing suggested that osmium-exposed A2780 cells undergo a metabolic shunt from glycolysis to oxidative phosphorylation, where defective machinery, associated with mutations in complex I, could enhance activity. Downstream events, measured by time-series reverse-phase protein microarrays, high-content imaging, and flow cytometry, showed a dramatic increase in mitochondrially produced reactive oxygen species (ROS) and subsequent DNA damage with up-regulation of ATM, p53, and p21 proteins. In contrast to platinum drugs, exposure to this organo-osmium compound does not cause significant apoptosis within a 72-h period, highlighting a different mechanism of action. Superoxide production in ovarian, lung, colon, breast, and prostate cancer cells exposed to three other structurally related organo-Os(II) compounds correlated with their antiproliferative activity. DNA damage caused indirectly, through selective ROS generation, may provide a more targeted approach to cancer therapy and a concept for next-generation metal-based anticancer drugs that combat platinum resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells

Hearn

Romero‐Canelón

Munro

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Radioresistant prostate cancer cells had lower baseline ROS, and ALDH+-derived xenograft tumor cells had high ALDH1A1 levels and low ROS production (15). ROS production is stimulated by irradiation and causes DNA damage (29)(30)(31). Interestingly, ROS-induced DNA damage has been implicated in gene regulation (32,33); thus it would be interesting to determine how ALDHs affect transcription of genes regulated in this manner.…”

Section: Figurementioning

confidence: 99%

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

2016

View full text Add to dashboard Cite

Resistance to current chemotherapeutic or radiation-based cancer treatment strategies is a serious concern. Cancer stem cells (CSCs) are typically able to evade treatment and establish a recurrent tumor or metastasis, and it is these that lead to the majority of cancer deaths. Therefore, a major current goal is to develop treatment strategies that eliminate the resistant CSCs as well as the bulk tumor cells in order to achieve complete disease clearance. Aldehyde dehydrogenases (ALDHs) are important for maintenance and differentiation of stem cells as well as normal development. There is expanding evidence that ALDH expression increases in response to therapy and promotes chemoresistance and survival mechanisms in CSCs. This perspective will discuss a paper by

show abstract

“…22 ROS may cause a wide spectrum of chromatin lesions through oxidation, nitration, halogenation and base alkylation, DNA interstrand crosslinking and DNA-protein crosslinking. 23 Due to spontaneous reactions or repair processes, these lesions may be converted into DNA breaks (DNA fragmentation), resulting in chromatin decondensation. Previous studies have reported similar chromatin damage in the spermatozoa of EtOH-consuming rats.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Occasional Alcohol Drinking on Semen Quality and Sperm Morphology among Young and Healthy Polish Men

Lwow¹,

Mędraś²,

Słowińska-Lisowska³

et al. 2017

JOMH

View full text Add to dashboard Cite

BackgroundEthanol (EtOH) is an agent that seems to exert an especially harmful effect on male fertility. The impact of high EtOH intake on fertility was demonstrated in numerous researches, with data suggesting that this effect may have been due to decreased semen quality; however, similar negative effects were not identified among occasional EtOH drinkers. There are currently no recommendations for alcohol consumption for men who plan to have a child other than avoiding high EtOH intake. Thus, studies on the effect of moderate and occasional EtOH drinking on semen quality are needed to develop appropriate recommendations for men planning to have a child in the future. The aim of this study was to determine whether changes in semen-quality parameters and sperm morphology occur in healthy young men who occasionally exceed the WHO-recommended weekly dose of EtOH but are not alcohol dependent and do not frequently consume high amounts of EtOH.

show abstract

DNA damage by reactive species: Mechanisms, mutation and repair

Cited by 292 publications

References 125 publications

Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells

Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

The Effect of Occasional Alcohol Drinking on Semen Quality and Sperm Morphology among Young and Healthy Polish Men

Contact Info

Product

Resources

About