Oxidative Damage to DNA in Non-Malignant Disease: Biomarker or Biohazard?

Evans, Mark D.; Cooke, Marcus S.

doi:10.1159/000092500

Cited by 12 publications

(10 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With impaired OGG1 function and/or expression, cells are not able to cleave damaged guanosine from DNA, resulting in decreased 8-OHdG serum levels, as observed in the present study. Similar results, i.e., low serum 8-OHdG levels compared with those in healthy control subjects, have been reported in certain benign diseases, such as Alzheimer disease and systemic lupus erythematosus, and in gastrointestinal carcinomas (9,22,23). The authors of these studies have suggested that low serum 8-OHdG levels should be taken as evidence of defective DNA repair in target tissue rather than low levels of oxidative damage.…”

Section: Discussionsupporting

confidence: 74%

“…They comprise a group of free radical and nonradical species that can be either harmful to or essential for living systems, depending mainly on their concentration (8,9). Therefore, antioxidant and other cell redox state-modulating enzyme systems are found in all cells, to maintain ROS production and degradation in balance (6).…”

mentioning

confidence: 99%

“…An excess of ROS is potent enough to damage cellular lipids, proteins, or DNA. Because of this, ROS have been linked to several pathologic conditions, such as carcinogenesis, chronic inflammation/infection, aging, and neurodegenerative and cardiovascular diseases (7)(8)(9). Because of their extremely short half-lives, most ROS are difficult to assess directly, and therefore specific markers of ROS-derived damage in various cellular compartments are used to measure oxidative stress.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Distinctively low levels of serum 8-hydroxydeoxyguanosine in women with polycystic ovary syndrome

Sova

Morin‐Papunen

Puistola

et al. 2010

Fertility and Sterility

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 74%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Distinctively low levels of serum 8-hydroxydeoxyguanosine in women with polycystic ovary syndrome

Sova

Morin‐Papunen

Puistola

et al. 2010

Fertility and Sterility

View full text Add to dashboard Cite

“…It is well established that the major portion of oxidative stress long term effects is inflicted by damage to DNA [32], [68], [69]. Conversely, FoxO proteins are known to act as major mediators of cell defense against oxidative stress by regulating the expression of proteins involved in ROS scavenging and repair of oxidative damage [28], [70].…”

Section: Resultsmentioning

confidence: 99%

KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species

et al. 2010

View full text Add to dashboard Cite

KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1−/− cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1−/− cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45α, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the cell capacity to scavenge intracellular ROS through an antioxidant pathway involving FoxO1 and SOD2, thus providing novel and useful insights into the understanding of KRIT1 molecular and cellular functions.

show abstract

“…Oxidative damage to DNA perhaps receives the most attention, for not only can this lead to mutation (Cheng, Cahill et al 1992), but it may have numerous other effects upon cell function, such as acceleration of telomere shortening, or modification of gene expression and cell signalling (Evans and Cooke 2004). Overall, this demonstrates that oxidative modification of DNA possesses clear mechanistic relevance to the pathogenesis of both malignant and non-malignant disease (Evans and Cooke 2006).…”

Section: Introductionmentioning

confidence: 99%

Interlaboratory comparison of methodologies for the measurement of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine

Cooke¹,

Barregård

Mistry³

et al. 2009

Biomarkers

View full text Add to dashboard Cite

Urinary 8-oxo-7,8-dihydro-2"-deoxyguanosine (8-oxodGuo) is widely used as a marker of oxidative stress. Herein we report the comparison of two, distinct chromatographic assays, with ELISA. Chromatographic assays displayed good agreement (r = 0.89, p < 0.0001), whereas there was markedly worse, albeit still significant, agreement with ELISA (HPLC-GC/MS: r=0.43, HPLC-EC: r=0.56; p<0.0001). Mean values differed significantly between chromatographic assays and ELISA (HPLC-GC/MS: 3.86, HPLC-EC: 4.20, ELISA: 18.70 ng/mg creatinine, p<0.0001). Whilst it is reassuring to note good agreement between chromatographic assay, this study reveals significant short-comings in the ELISA, which bring into question its continued use in its present form.

show abstract

Oxidative Damage to DNA in Non-Malignant Disease: Biomarker or Biohazard?

Cited by 12 publications

References 25 publications

Distinctively low levels of serum 8-hydroxydeoxyguanosine in women with polycystic ovary syndrome

Distinctively low levels of serum 8-hydroxydeoxyguanosine in women with polycystic ovary syndrome

KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species

Interlaboratory comparison of methodologies for the measurement of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine

Contact Info

Product

Resources

About