Alkaline, Endo III and FPG modified comet assay as biomarkers for the detection of oxidative DNA damage in rats with experimentally induced diabetes

Kushwaha, Sapana; Vikram, Ajit; Trivedi, P.P.; Jena, Gopabandhu

doi:10.1016/j.mrgentox.2011.10.004

Cited by 52 publications

(35 citation statements)

References 46 publications

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“…Oxidative damage to bases can be determined using modified Comet assays, which use repair endonucleases to assess specific types of damage. An increase in endonuclease III-sensitive sites, indicative of oxidized pyrimidine bases, was observed in type 2 diabetes, while an increase in fpg-sensitive sites, indicative of oxidized purines, was found in some but not all studies [13], [28], [29]. In our study, while fpg-modified oxidative DNA damage was higher in pancreatic cancer patients compared to both control groups, the increase was not statistically significant.…”

Section: Discussioncontrasting

confidence: 70%

“…These parameters have previously been investigated in human diabetic subjects and in an animal model of diabetes [13], [14], [28], [29]; however, to date this is the first report of these parameters in pancreatic cancer patients. In type 2 diabetic patients, decreased TAC and increased plasma MDA was observed, compared to subjects with normal glucose tolerance [14].…”

Section: Discussionmentioning

confidence: 99%

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Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility

Hocevar

Kamendulis

et al. 2014

PLoS ONE

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Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00±0.05) versus both healthy unrelated and related controls (0.70±0.06, p<0.001 and 0.82±0.07, p = 0.046, respectively). Analysis of 22 selected SNPs in oxidative stress and DNA damage genes revealed that CYP2A6 L160H was associated with pancreatic cancer. In addition, DNA damage was found to be associated with TNFA −308G>A and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility

Hocevar

Kamendulis

et al. 2014

PLoS ONE

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“…The mechanism underlying atherogenesis in T2DM has been under extensive investigation. Studies have shown that oxidative stress plays a key role in this process [17]–[20]. Reactive oxygen species (ROS) can lead to damage of endothelial cells and to proliferation, migration and phenotypic change of smooth muscle cells, contributing to atherogenesis in the setting of DM [21], [22].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Aorta and Protective Effects of Grape Seed Procyanidin B2 in db/db Mice Reveal a Critical Role of Milk Fat Globule Epidermal Growth Factor-8 in Diabetic Arterial Damage

et al. 2012

PLoS ONE

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BackgroundAtherosclerosis is one of the major complications of type 2 diabetic patients (T2DM), leading to morbidity and mortality. Grape seed procyanidin B2 (GSPB2) has demonstrated protective effect against atherosclerosis, which is believed to be, at least in part, a result of its antioxidative effects. The aim of this study is to identify the target protein of GSPB2 responsible for the protective effect against atherosclerosis in patients with DM.Methods and ResultsGSPB2 (30 mg/kg body weight/day) were administrated to db/db mice for 10 weeks. Proteomics of the aorta extracts by iTRAQ analysis was obtained from db/db mice. The results showed that expression of 557 proteins were either up- or down-regulated in the aorta of diabetic mice. Among those proteins, 139 proteins were normalized by GSPB2 to the levels comparable to those in control mice. Among the proteins regulated by GSPB2, the milk fat globule epidermal growth factor-8 (MFG-E8) was found to be increased in serum level in T2DM patients; the serum level of MFG-E8 was positively correlated with carotid-femoral pulse wave velocity (CF-PWV). Inhibition of MFG-E8 by RNA interference significantly suppressed whereas exogenous recombinant MFG-E8 administration exacerbated atherogenesis the db/db mice. To gain more insights into the mechanism of action of MFG-E8, we investigated the effects of MFG-E8 on the signal pathway involving the extracellular signal-regulated kinase (ERK) and monocyte chemoattractant protein-1 (MCP-1). Treatment with recombinant MFG-E8 led to increased whereas inhibition of MFG-E8 to decreased expression of MCP-1 and phosphorylation of ERK1/2.ConclusionOur data suggests that MFG-E8 plays an important role in atherogenesis in diabetes through both ERK and MCP-1 signaling pathways. GSPB2, a well-studied antioxidant, significantly inhibited the arterial wall changes favoring atherogenesis in db/db mice by down-regulating MFG-E8 expression in aorta and its serum level. Measuring MFG-E8 serum level could be a useful clinical surrogate prognosticating atherogenesis in DM patients.

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“…After entering cells, PQ acts as a redox-cycling compound in the cytosol, and potentially leads to indirect mitochondrial toxicity [8]. ROS production culminates in oxidative damage to macromolecules such as lipids and proteins [9]. Furthermore, PQ-induced ROS production causes DNA damage: single-and double-strand DNA breaks, base modifications, deoxyribose fragmentation, DNA -protein cross-links, and abasic sites [10,11].…”

Section: Introductionmentioning

confidence: 99%