DNA Damage, n-3 Long-Chain PUFA Levels and Proteomic Profile in Brazilian Children and Adolescents.

Fatty acids play a significant role in maintaining cellular and DNA protection and we previously found an inverse relationship between blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DNA damage. The aim of this study was to explore differences in proteomic profiles, for 117 pro-inflammatory proteins, in two previously defined groups of individuals with different DNA damage and EPA and DHA levels. Healthy children and adolescents (n = 140) aged 9 to 13 years old in an urban area of Brazil were divided by k-means cluster test into two clusters of DNA damage (tail intensity) using the comet assay (cluster 1 = 5.9% ± 1.2 and cluster 2 = 13.8% ± 3.1) in our previous study. The cluster with higher DNA damage and lower levels of DHA (6.2 ± 1.6 mg/dL; 5.4 ± 1.3 mg/dL, p = 0.003) and EPA (0.6 ± 0.2 mg/dL; 0.5 ± 0.1 mg/dL, p < 0.001) presented increased expression of the proteins CDK8-CCNC, PIK3CA-PIK3R1, KYNU, and PRKCB, which are involved in pro-inflammatory pathways. Our findings support the hypothesis that low levels of n-3 long-chain PUFA may have a less protective role against DNA damage through expression of pro-inflammatory proteins, such as CDK8-CCNC, PIK3CA-PIK3R1, KYNU, and PRKCB.

DNA damage is inversely associated to blood levels of DHA and EPA fatty acids in Brazilian children and adolescents.

This study aimed to investigate the association between DNA damage and blood levels of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), retinol, beta-carotene and riboflavin in Brazilian children and adolescents. Subjects (n = 140) were healthy boys and girls aged 9 to 13 years in Ribeirão Preto (SP, Brazil). Data collection included anthropometry, assessment of energy intake and blood sampling. DNA damage was evaluated by single-cell gel electrophoresis (comet assay). Principal component analysis (PCA) was used to verify associations between blood concentrations of vitamins, polyunsaturated fatty acids and DNA damage. Multiple regression analyses, k-means cluster, and analysis of covariance (ANCOVA), adjusted for confounding variables such as age, sex, energy intake, body mass index and total cholesterol (when needed), were applied to confirm the associations. PCA explained 69.4% of the inverse relationships between DNA damage and blood levels of DHA, EPA, retinol, and beta-carotene. Results were confirmed by ANCOVA and multiple regression analyses for DHA and EPA. In conclusion, omega-3-fatty acids were inversely associated with DNA damage in Brazilian children and adolescents and may be a protective factor against the development of future diseases.

The cosmetic dye quinoline yellow causes DNA damage in vitro.

Quinoline yellow (QY) is a chinophthalon derivative used in cosmetic compositions for application to the skin, lips, and/or body surface. However, regulatory data about the genotoxicity and/or mutagenicity of this compound are still controversial. Therefore, this work evaluated the genotoxicity of QY using the comet assay and the cytokinesis-block micronucleus cytome assay (CBMN-Cyt) in the metabolically competent cell line HepG2, which closely mimics phase I metabolism. This research also identified the products formed after electrochemical oxidation of the QY dye, which simulates hepatic biotransformation. The primary products generated after the oxidation process were analyzed by High Performance Liquid Chromatography coupled with a Diode Array Detector (HPLC/DAD), which detected the production of 4,4'-diaminodiphenylmethane, 2-methoxy-5-methylaniline and 4,4'-oxydianiline. The results demonstrated that low (from 0.5 to 20 µg mL(-1)) QY concentrations were genotoxic in HepG2 cells on both assays and those harmful compounds were detected after the oxidation process. Our findings suggest that this colorant could cause harmful effects to humans if it is metabolized or absorbed through the skin.

Transgenic and conventional Brazilian soybeans don't cause or prevent preneoplastic colon lesions or oxidative stress in a 90-day in vivo study / Sojas transgênicas e convencionais brasileiras não causam ou previnem lesões pré-neoplásicas ou stress oxidativo em estudo in vivo de 90 dias

OBJECTIVE: The study presents the results of a 90-day safety assessment of rats fed with four varieties of soybeans, BRS 245 RR and BRS Valiosa RR (transgenic), BRS 133 and MG BR46 Conquista (non-transgenic). METHODS: Diets were prepared by incorporating toasted soybean flour to a commercial diet at 1%, 10% or 20% weight In the in vivo experimental the rats' body weight, body weight gain, food consumption, number of aberrant crypt foci, oxidative stress biomarkers, urea and creatinine levels were analyzed and compared between experimental groups, as well as histopathological observations (digestive tract, liver, kidneys). RESULTS: The results indicate that glyphosate-tolerant soy varieties neither induce nor prevent aberrant crypt foci induction, nor do their conventional counterparts. Similarly, none of the four soybean varieties tested induced changes in the digestive tract, liver or kidney. Serum biochemical parameters were also unchanged. CONCLUSION: The consumption of both, conventional and transgenic soybeans, were insufficient to ameliorate dimethylhydrazine-induced oxidative stress.

OBJETIVO: Este estudo apresenta os resultados de um experimento de 90 dias com o objetivo de avaliar a segurança de quatro variedades de grãos de soja: BRS 245 RR e BRS Valiosa RR (transgênicas), BRS 133 e MG BR46 Conquista (não transgênicas). MÉTODOS: As dietas foram preparadas incorporando farinha de grãos de soja à dieta comercial (FRI-LAB Ratos II) a 1%, 10% ou 20% m/m. O peso corpóreo dos animais, o ganho de peso, o consumo de dieta, o número de focos de criptas aberrantes e os níveis de marcadores de estresse oxidativo, de creatinina e de ureia foram comparados entre os grupos experimentais, assim como as observações histopatológicas (trato digestivo, fígado e rins). RESULTADOS: Os resultados indicaram que as variantes glifosato-tolerantes não induziram ou preveniram a indução de focos de criptas aberrantes, assim como suas parentais convencionais. Similarmente, nenhuma das quatro variedades de grãos de soja testadas induziu alterações no trato digestivo, no fígado e nos rins. Os parâmetros bioquímicos do soro permaneceram também inalterados. CONCLUSÃO: Tanto o consumo de grãos de soja convencionais quanto o de transgênicos foram ineficazes para melhorar os níveis de estresse oxidativo induzidos pela dimetilhidrazina.

Coenzyme Q10 protects Pc12 cells from cisplatin-induced DNA damage and neurotoxicity.

The purpose of this study was to investigate the neuroprotective effect of a water-soluble formulation of coenzyme Q10 (WS-CoQ10) in PC12 cells exposed to cisplatin, a chemotherapeutic agent with a dose-limiting factor due to neurotoxicity. In the cytokinesis-block micronucleus cytome assay (CBMN Cyt), WS-CoQ10 (at concentrations of 0.1, 0.5 and 1.0µgmL(-1)) protected PC12 cells from cisplatin-induced DNA damage (0.1µgmL(-1)), reducing the frequency of micronuclei (MNi) and nuclear buds (NBUDs). WS-CoQ10 did not alter the mRNA expression levels of Tp53 (at a concentration of 1.0µgmL(-1)) and exhibited neuroprotective activity by stimulating cisplatin-inhibited neurite outgrowth in nerve growth factor (NGF)-differentiated PC12 cells (at a concentration of 0.1µgmL(-1)). In conclusion, WS-CoQ10 protected the PC12 cells from cisplatin-induced DNA damage and neurotoxicity. Moreover, the neuroprotective effects of WS-CoQ10 suggest a possible application in chemotherapeutic protocols.

Genotoxic and mutagenic effects of erythrosine B, a xanthene food dye, on HepG2 cells.

Erythrosine (ErB) is a xanthene and an US Food and Drug Administration approved dye used in foods, drugs and cosmetics. Although its utilization is permitted, ErB is described as inhibitor of enzymes and protein-protein interactions and is toxic to pituitary and spermatogenesis processes. However, the genotoxicity and mutagenicity of ErB is inconclusive in the literature. This study aimed to analyze the genotoxicity of this dye using the alkaline comet assay and is the first investigation to evaluate ErB mutagenicity using the cytokinesis block micronucleus cytome (CBMN-Cyt) assay in HepG2 cells. These cells were chosen because they produce phase I and phase II enzymes that can mimic in vivo metabolism. The cells were treated with seven concentrations (0.1-70.0 µg mL(-1)) of ErB, and the results showed genotoxicity at the two highest concentrations and mutagenicity at six concentrations. Furthermore, as micronuclei result from clastogenic and aneugenic processes, while comet assay is often considered more sensitive and detects DNA single strain breaks, we suggest that an aneugenic is responsible for the observed damage. Although ErB is approved for use in the food, cosmetic and pharmaceutical industries, it must be used carefully because it damages the DNA structure.