Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid

Gómez‐Meda, Belinda Claudia; Zamora‐Pérez, Ana Lourdes; Muñoz-Magallanes, T.; Sánchez-Parada, María Guadalupe; Banuelos, Jésus; Guerrero-Velázquez, Celia; Sánchez-Orozco, Laura V.; Vera-Cruz, José María; Armendáriz‐Borunda, Juan; Zúñiga‐González, Guillermo Moisés

doi:10.1016/j.mrgentox.2015.12.003

Cited by 18 publications

(5 citation statements)

References 56 publications

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“…Additionally, a linear correlation was detected between HbA1c and scored MN, which was particularly pronounced in patients with HbA1c > 7.5%. These results are supported by two recent publications which reported higher MN frequencies compared to healthy controls and an HbA1c-dependent increase of genomic instabilities 13 15 . In addition, several studies showed an increased cancer risk in diabetes patients compared to respective controls 6 16 17 18 19 20 21 22 23 .…”

Section: Discussionsupporting

confidence: 87%

Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients

Grindel

Brath²,

Nersesyan³

et al. 2017

Sci Rep

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Diabetes Mellitus type 2 (DM2) is associated with increased cancer risk. Instability of the genetic material plays a key role in the aetiology of human cancer. This study aimed to analyse genomic instability with the micronucleus cytome assay in exfoliated buccal cells depending on glycated haemoglobin (HbA1c) levels and medication in 146 female DM2 patients. The occurrence of micronuclei was significantly increased in DM2 patients compared to healthy controls. Furthermore, it was doubled in DM2 patients with HbA1c > 7.5% compared to subjects with HbA1c ≤ 7.5%. Positive correlations were found between micronuclei frequencies and HbA1c as well as fasting plasma glucose. Patients under insulin treatment showed a two-fold increase in micronuclei frequencies compared to subjects under first-line medication (no drugs or monotherapy with non-insulin medication). However, after separation of HbA1c (cut-off 7.5%) only patients with severe DM2 characterised by high HbA1c and insulin treatment showed higher micronuclei frequencies but not patients with insulin treatment and low HbA1c. We demonstrated that the severity of DM2 accompanied by elevated micronuclei frequencies predict a possible enhanced cancer risk among female DM2 patients. Therapy, therefore, should focus on a strict HbA1c control and personalised medical treatments.

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Section: Discussionsupporting

confidence: 87%

Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients

Grindel

Brath²,

Nersesyan³

et al. 2017

Sci Rep

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“…The results found in our study align with [18], as we also observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before folic acid supplementation vs. 11.18 ± 7.42 at 15 days of supplementation and 9.11 ± 10.9 at 30 days of supplementation), with a decrease in the frequency of all evaluated nuclear abnormalities, with statistical significance in NBUDs, CC, KX, PNs, and BNs.…”

Section: Effect Of Folic Acid Supplementation On the Occurrence Of Nu...supporting

confidence: 91%

“…They also found a decrease in nuclear abnormalities (NAs) before and after folic acid supplementation (20.4 ± 8.0 before treatment vs. 10.5 ± 5.2 after treatment). They attribute the statistically significant decrease in NAs (MNs, BNs, PNs, KX, KX+CC, KL, NBUDs) to folic acid supplementation [18].…”

Section: Effect Of Folic Acid Supplementation On the Occurrence Of Nu...mentioning

confidence: 99%

“…Additionally, it shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and restoring the bioavailability of nitric oxide by interacting with nitric oxide synthase and increasing the availability of the cofactor tetrahydrobiopterin [17]. There is scientific evidence demonstrating the antioxidant effect of folic acid in improving genetic damage through its protective effect, as evidenced by the reduction in the frequency of nuclear abnormalities [18].…”

Section: Introductionmentioning

confidence: 99%

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Amelioration of Cytogenotoxic Damage in Drug Abusers Supplemented with Folic Acid

Gómez-Cabrera,

González-Santiago,

Rodríguez-Mora

et al. 2024

Biomedicines

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Background: Cytogenotoxic damage caused by the consumption of legal and illegal drugs in drug abusers has been demonstrated, primarily due to alterations in their antioxidant capacity, cellular repair mechanisms, and increased production of free radicals. Folic acid shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and reducing genomic damage. Methods: The intervention involved administering 15 mg of folic acid, divided into three doses per day, to a group of 44 drug abusers. The frequency of nuclear abnormalities (NAs) was determined; micronuclei (MNs), nuclear buds (NBUDs), binucleated cells (BNs), abnormally condensed chromatin (CC), karyorrhexis (KX), pyknotic nuclei (PNs), and karyolysis (KL) were determined at different pre-treatment (baseline) and post-treatment time points at 15 and 30 days. Additionally, a group of 44 healthy individuals was used as the control group. Results: We observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before supplementation vs. 11.18 ± 7.42 at 15 days and 9.11 ± 10.9 at 30 days of supplementation). Specifically, it decreased the frequency of NBUDs, BNs, CC, KX, and PNs (p < 0.05). Conclusion: Our study demonstrates a clear improvement in cytogenotoxic damage in drug abusers supplemented with folic acid.

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“…Therefore, based on the results observed in this study, folic acid deficiency in T2D may potentiate the genotoxic effects of elevated glucose concentrations which may be associated with increased cancer risk observed in these individuals. In support of this, several studies have shown a decrease in MNi frequency of T2D following folic acid supplementation [ 49 , 50 ]. However, whether this has any effect on cancer incidence has not been previously reported.…”

Section: Discussionmentioning

confidence: 70%

Folic acid deficiency increases sensitivity to DNA damage by glucose and methylglyoxal

et al. 2022

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Type 2 diabetes (T2D) is associated with elevated frequencies of micronuclei (MNi) and other DNA damage biomarkers. Interestingly, individuals with T2D are more likely to be deficient in micronutrients (folic acid, pyridoxal-phosphate, cobalamin) that play key roles in one-carbon metabolism and maintaining genomic integrity. Furthermore, it has recently been shown that deficiencies in these nutrients, in particular folic acid leaves cells susceptible to glucose-induced DNA damage. Therefore, we sought to investigate if the B lymphoblastoid WIL2-NS cell line cultured under folic acid-deficient conditions was more sensitive to DNA damage induced by glucose, or the reactive glycolytic byproduct methylglyoxal (MGO) and subsequent advanced glycation endproduct formation. Here, we show that only WIL2-NS cultured under folic acid-deficient conditions (23 nmol/l) experience an increase in MNi frequency when exposed to high concentrations of glucose (45 mmol/l) or MGO (100 µmol/l). Furthermore, we showed aminoguanidine, a well-validated MGO and free radical scavenger was able to prevent further MNi formation in folic acid-deficient cells exposed to high glucose, which may be due to a reduction in MGO-induced oxidative stress. Interestingly, we also observed an increase in MGO and other dicarbonyl stress biomarkers in folic acid-deficient cells, irrespective of glucose concentrations. Overall, our evidence shows that folic acid-deficient WIL2-NS cells are more susceptible to glucose and/or MGO-induced MNi formation. These results suggest that individuals with T2D experiencing hyperglycemia and folic acid deficiency may be at higher risk of chromosomal instability.

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Nuclear abnormalities in buccal mucosa cells of patients with type I and II diabetes treated with folic acid

Cited by 18 publications

References 56 publications

Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients

Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients

Amelioration of Cytogenotoxic Damage in Drug Abusers Supplemented with Folic Acid

Folic acid deficiency increases sensitivity to DNA damage by glucose and methylglyoxal

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