Induction and removal of DNA damage in blood leukocytes of patients with type 2 diabetes mellitus undergoing hemodialysis

Bagatini, Pamela Brambilla; Palazzo, Roberta Passos; Rodrigues, Manoela Tressoldi; Costa, Cynthia Hernandes; Maluf, Sharbel Weidner

doi:10.1016/j.mrgentox.2008.08.004

Cited by 22 publications

(15 citation statements)

References 30 publications

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“…No correlations between DNA damage endpoints and age, FPG, or A1C were observed. Several studies have shown that there is no increase in DNA damage in DM2 [21, 22]. Other studies have indicated that an increase in micronuclei will not likely occur in early DM2 [23], but only in uncompensated DM2 (i.e., A1C > 8%) [24].…”

Section: Discussionmentioning

confidence: 99%

Vitamin C Intake Reduces the Cytotoxicity Associated with Hyperglycemia in Prediabetes and Type 2 Diabetes

Franke

Müller

Santos

et al. 2013

BioMed Research International

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Hyperglycemia leads to the formation of free radicals and advanced glycation end-products (AGEs). Antioxidants can reduce the level of protein glycation and DNA damage. In this study, we compared the levels of vitamin C intake, which is among the most abundant antioxidants obtained from diet, with the levels of fasting plasma glucose (FPG), glycated hemoglobin (A1C), DNA damage, and cytotoxicity in prediabetic subjects and type 2 diabetic subjects. Our results indicated that there was no significant correlation between FPG or A1C and DNA damage parameters (micronuclei, nucleoplasmic bridges, and nuclear buds). FPG and A1C correlated with necrosis (r = 0.294; P = 0.013 and r = 0.401; P = 0.001, resp.). Vitamin C intake correlated negatively with necrosis and apoptosis (r = −0.246; P = 0.040, and r = −0.276; P = 0.021, resp.). The lack of a correlation between the FPG and A1C and DNA damage could be explained, at least in part, by the elimination of cells with DNA damage by either necrosis or apoptosis (cytotoxicity). Vitamin C appeared to improve cell survival by reducing cytotoxicity. Therefore, the present results indicate the need for clinical studies to evaluate the effect of low-dose vitamin C supplementation in type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Vitamin C Intake Reduces the Cytotoxicity Associated with Hyperglycemia in Prediabetes and Type 2 Diabetes

Franke

Müller

Santos

et al. 2013

BioMed Research International

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“…found no changes in DNA breaks and oxidative DNA lesions during the HD session, when performing the comet assay on whole blood in a small substudy (n = 9). Bagatini et al . observed increased levels of DNA breaks after dialysis compared to before dialysis when analysing whole blood with comet assay.…”

Section: Discussionmentioning

confidence: 99%

The effects of hemodialysis treatment on the level of DNA strand breaks and oxidative DNA lesions measured by the comet assay

Ersson

Odar‐Cederlöf

Fehrman-Ekholm

et al. 2012

Hemodialysis International

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Hemodialysis patients have a higher risk for oxidative stress-related complications, such as cardiovascular disease and cancer. The increased level of oxidative stress is due to several factors, e.g., the hemodialysis treatment itself and the uremic state. In the present study, the effects of dialysis treatment on the level of DNA breaks and oxidative DNA lesions in mononuclear cells were measured with the comet assay. Factors possibly affecting DNA damage (reported as % DNA in tail) such as the duration of dialysis, time since last dialysis session, years of dialysis treatment, nutritional status (measured as protein catabolic rate), age, and diabetes were also investigated. The levels of DNA breaks (13.6 ± 4.7 before dialysis) and oxidative DNA lesions (7.9 ± 4.8 before dialysis) were significantly higher in dialysis patients (n = 31) compared to the levels of DNA breaks (5.8 ± 1.1) and oxidative DNA lesions (3.4 ± 1.7) in 10 healthy controls (P < 0.001). A decrease of DNA breaks was observed after dialysis (P = 0.038), and the level of oxidative DNA lesions was higher when the time between two treatment sessions were 68 hours compared to 44 hours (P < 0.001). Older subjects had a higher level of DNA breaks (P = 0.003), a good nutritional status predicted a lower level of DNA breaks (P < 0.001), and the duration of the dialysis session was inversely correlated with oxidative DNA lesions (P = 0.014). Diabetes or years of dialysis treatment did not affect DNA damage. The observations in the present study suggest that accumulation of uremic toxins induce DNA damage. The hemodialysis treatment seems to change the DNA damage.

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“…(19) A recent study conducted by our research team (12) found that two factors play an important role in the increase of DNA damage in hemodialysis patients with DM2: the disease itself, which leads to the accumulation of metabolites that damage DNA and hemodialysis, which removes metabolites but also increases the level of DNA damage in filtered cells. Thus, the amount of DNA damage in hemodialysis patients varies substantially during one week.…”

Section: Discussionmentioning

confidence: 99%

“…The results indicated a very significant weekly variation which is influenced by the accumulation of metabolites and the hemodialysis sessions. (12) Although it was shown that these patients have increased DNA damage as identified by the comet assay, this damage may be transient as the test is unable to detect genomic instability after cellular division cycles.…”

Section: Introductionmentioning

confidence: 99%

Genomic instability in patients with type 2 diabetes mellitus on hemodialysis

Palazzo¹,

Bagatini²,

Schefer³

et al. 2011

Rev. Bras. Hematol. Hemoter.

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ObjectiveA previous study by our research group evaluated the levels of DNA damage using the comet assay in hemodialysis patients with type 2 diabetes mellitus. The same blood samples were also evaluated using the cytochalasin B micronucleus assay. A comparison of the results of the two assays is presented here.MethodsWhole blood samples were collected from 22 type 2 diabetes mellitus patients on hemodialysis and from 22 control subjects. Samples were collected from patients early in the morning on Mondays, before the first weekly hemodialysis session. The cytokinesis-block micronucleus assay (CBMN) was used to evaluate genomic instability.ResultsThe frequencies of micronuclei and nuclear buds were higher in patients than in controls (p-value = 0.001 and p-value < 0.001, respectively). There was a correlation between the frequency of micronuclei and DNA damage with the results of the comet assay (p-value < 0.001). The difference in the frequency of micronuclei and nuclear buds between patients and controls was more pronounced in the group with higher median comet values than in the group with lower comet values.ConclusionOur results suggest that the increased rates of DNA damage as measured by the comet assay and influenced by the weekly routine therapy of these patients has a mutagenic effect, thereby increasing the risk of cancer in this group.

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Induction and removal of DNA damage in blood leukocytes of patients with type 2 diabetes mellitus undergoing hemodialysis

Cited by 22 publications

References 30 publications

Vitamin C Intake Reduces the Cytotoxicity Associated with Hyperglycemia in Prediabetes and Type 2 Diabetes

Vitamin C Intake Reduces the Cytotoxicity Associated with Hyperglycemia in Prediabetes and Type 2 Diabetes

The effects of hemodialysis treatment on the level of DNA strand breaks and oxidative DNA lesions measured by the comet assay

Genomic instability in patients with type 2 diabetes mellitus on hemodialysis

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