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Jeffamines ® are a family of polymers containing primary amine groups attached to the extremities of polyether backbone which can be used as biomaterials. They have been used in combination with polyethylenimine (PEI) to improve biocompatibility in drug and gene delivery systems. Despite these facts, very few studies have been done on cytotoxicity and genotoxicity of pure Jeffamines ® or compared with PEI. The present study aimed to evaluate and compare the cytotoxic and genotoxic effects of Jeffamines ® and PEI in CHO-K1 cells. Specifically, polypropylene oxide 2000 (PPO 2000, Jeffamine ® D series), polyethylene oxide 1900 (PEO 1900, Jeffamine ® ED series), branched 25 kDa PEI, and linear 20 kDa PEI were evaluated at different concentrations. Cell viability and proliferation were assessed by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and 5-bromo-2'-deoxyuridine (BrdU) assays, respectively. Genotoxicity was evaluated using single cell gel electrophoresis assay and the cytokinesis-blocked micronucleus assay. PPO 2000 was the most cytotoxic Jeffamine ® , whereas PEO 1900 did not caused significant cell death at any tested concentration. Branched PEI was more cytotoxic than linear PEI (LPEI) and both were more cytotoxic than Jeffamines ® . Only PPO 2000 induced DNA damage when evaluated in comet assay probably due to its cytotoxicity. PPO 2000, PEO 1900, and PEI did not increase the frequency of micronuclei when tested at sub-cytotoxic concentrations. This work provides new insights about biocompatibility of Jeffamines ® and PEI and suggests the genotoxicological safety for further investigations of PEO 1900 in drug and gene delivery systems. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 742-750, 2018., (© 2017 Wiley Periodicals, Inc.)

The high consumption of fructose is linked to the increase in various characteristics of the metabolic syndrome. Fish oil is beneficial for the treatment of these comorbidities, such as insulin resistance, dyslipidemia, and hepatic steatosis. The objective of this study was to evaluate the consequences of the administration of fish oil concomitant to fructose ingestion during the experiment (45 days) and during the final 15 days in high-fructose-fed rats. Male Wistar rats were divided into 5 groups: control; those receiving 10% fish oil (FO); those receiving 60% fructose (Fr); those receiving 60% fructose and 10% fish oil for 45 days (FrFO); and those receiving fructose plus soybean oil for 30 days and fish oil for the final 15 days of the study (FrFO15). There was an increase in triacylglycerol, serum total cholesterol, and hepatic volume in the Fr group. The FO and FrFO groups experienced an increase in lipid peroxidation and a decrease in serum reduced glutathione. The FrFO group suffered greater hepatic injury, with increased alanine aminotransferase levels and DNA damage. Marked n-3 incorporation occurred in the groups receiving fish oil, favoring a better response to the oral glucose tolerance test. Fructose induced comorbidities of the metabolic syndrome, and the use of fish oil promoted a better glucose tolerance, although it was accompanied by more hepatocyte damage.

A very appropriate method for antigenotoxicity evaluation of antioxidants is the comet assay, since this analytical method detects initial DNA lesions that are still subject to repair; in other words, lesions that are very associated to damages resulting from the generation and subsequent action of reactive species. However, a solid evaluation should be developed in order to avoid inexact interpretations. In our study, besides the association of curcumin with cisplatin, curcumin and cisplatin agents were also tested separately. Classical genotoxic compounds, when tested by the comet assay, present an increase in the nucleoid tail; however, the cisplatin treatment has resulted in a decrease of DNA migration. This was an expected effect, as the cross-links between cisplatin and DNA decrease the DNA electrophoretic mobility. A similar effect was observed with the curcumin treatment, which decreased the nucleoid tail. Such effect was not expected and reinforced the necessity of including in the study, separate treatment groups with potentially antigenotoxic substances. The comet assay results have been analyzed using specific software for image analysis, as well as the classical visual analysis, and we have observed that the effect of decrease in DNA electrophoretic mobility was more easily observed when the data were analyzed by the software.

Casearia sylvestris is used in Brazil as a popular medicine to treat ulcer, inflammation and tumour. Caseargrewiin F is a clerodane diterpene isolated from the ethanolic leaf extract of C.sylvestris. The aim of the study was to assess the capacity of the ethanolic extract of C.sylvestris leaves and caseargrewiin F to protect DNA and verify if both the compounds cause some DNA damage, using the micronucleus (MN) test and comet assay in mice. Balb-C mice were treated with the extract [3.13, 6.25, 12.5, 25, 50 and 75 mg/kg body weight (b.w.)] and caseargrewiin F (0.16, 0.32, 0.63, 1.3, 2.5 and 3.8 mg/kg b.w.) for 14 days. On day 15, DNA damage was induced by intra-peritoneal (i.p.) injection of cyclophosphamide (CP) (i.p.) at 50 mg/kg b.w. after the MN test and comet assay were performed. A protective effect of ethanolic extract was observed in MN test (6.25 and 12.5 mg/kg b.w.) and the comet assay (3.13 and 6.25, 12.5 and 25 mg/kg b.w.). Caseargrewiin F showed protective effect at 0.63, 1.3 and 2.5 mg/kg b.w. only in comet assay. We also tested the ability of compounds of C.sylvestris to induce MN and to increase the comet assay tail moment. The experimental design was similar to the DNA protection assay except that in test groups we omitted the CP challenge. We observed increased damage at 50 and 75 mg/kg b.w. of ethanolic extract of C.sylvestris and caseargrewiin F at 3.18 mg/kg b.w. in both the MN test and comet assay. We conclude that ethanolic extract of C. sylvestris and caseargrewiin F can protect cells against DNA damage induced by CP at low concentrations, but at high concentrations these compounds also induce DNA damage.

Breast cancer continues to be the major cause of cancer death among women. The high genetic heterogeneity and chemoresistant phenotypes of breast tumors require the search for new compounds to expand the options for the treatment of this disease. Kaurenoic acid (KA) is an ent‐kaurane type‐diterpene with cytotoxic and genotoxic effects against gastric and cervical cancer cells. In the present study, we report the antiproliferative effects of KA in the breast tumoral cell line MCF‐7 and the normal breast counterpart MCF‐10 A. The long‐term cytotoxic effects of KA were observed by the reduction of survival fraction at 50 and 100 μM. At these concentrations, the treatment with KA increased the extension of DNA damage followed by G1 cell cycle phase accumulation and induction of apoptosis in both cell lines. Taken together, the results contained herein support the promising antiproliferative effects of KA. [ABSTRACT FROM AUTHOR]

A very appropriate method for antigenotoxicity evaluation of antioxidants is the comet assay, since this analytical method detects initial DNA lesions that are still subject to repair; in other words, lesions that are very associated to damages resulting from the generation and subsequent action of reactive species. However, a solid evaluation should be developed in order to avoid inexact interpretations. In our study, besides the association of curcumin with cisplatin, curcumin and cisplatin agents were also tested separately. Classical genotoxic compounds, when tested by the comet assay, present an increase in the nucleoid tail; however, the cisplatin treatment has resulted in a decrease of DNA migration. This was an expected effect, as the cross-links between cisplatin and DNA decrease the DNA electrophoretic mobility. A similar effect was observed with the curcumin treatment, which decreased the nucleoid tail. Such effect was not expected and reinforced the necessity of including in the study, separate treatment groups with potentially antigenotoxic substances. The comet assay results have been analyzed using specific software for image analysis, as well as the classical visual analysis, and we have observed that the effect of decrease in DNA electrophoretic mobility was more easily observed when the data were analyzed by the software. [ABSTRACT FROM AUTHOR]

Abstract: Lycopene is a natural carotenoid, free radical scavenger, and presents protective effects by inhibiting oxidative DNA damage. The objective of the current study was to investigate the cytogenetic effects of a single acute and four daily gavage administrations of lycopene, and to examine possible protective effects on chromosomal damage induced by the antitumor drug cisplatin (cDDP) in rat bone marrow cells. The animals were divided into treatment groups, with three lycopene doses in the acute treatment (2, 4, and 6mg/kgb.w.), three lycopene doses in the subacute treatment (0.5, 1.0, and 1.5mg/kgb.w.) with and without cDDP (5mg/kgb.w. i.p.), and respective controls. The results indicated that lycopene is neither cytotoxic nor clastogenic when compared with the negative controls (p >0.01). cDDP-treated animals submitted to acute and subacute treatments with different lycopene doses showed a significant reduction (p <0.01) in the number of abnormal metaphases when compared with the animals treated only with cDDP. The protective effects of lycopene on cDDP-induced chromosomal damage may be attributed to its antioxidant activity. These results suggest that this carotenoid may prove useful in reducing some of the toxic effects associated with certain classes of chemotherapeutic agents. [Copyright &y& Elsevier]

• The baseline frequencies of cell damage and cell death measured by BMCyt assay were determined for Brazilian people. • Chromosomal stability in buccal cells was different among Brazilian regions but not affected by habits. • Chromosomal damage in buccal cells was influenced by age and equal for women and men. • The BMCyt assay is a good biomarker to smokers. The Buccal Micronucleus Cytome Assay (BMCyt) has become an important biomonitoring tool for assessing cytogenetic damage in many studied populations. Each laboratory applies protocols that vary according to the method of collecting and preparing samples. Besides, Brazil is a country of great territorial extensions that received immigrants from various parts of the world with different genetic backgrounds. Therefore, the present study aimed to evaluate the inter-laboratory variation in scoring the same set of slides using the more comprehensive scoring criteria, to standardize the BMCyt protocol, to observe the basal alterations in populations of different Brazilian regions and to compare it with other places around the world. Our results showed that a valuable number of laboratories participated, ten laboratories from different regions of the country, for the validation of the BMCyt in human biomonitoring studies, resulting in the 804 healthy individuals. This was possible because we observed: a range of measures needs to be considered, such as the baseline frequency of DNA damage and cell death in non-exposed individuals; age when grouped showed an influence on DNA damage, although when evaluated by group we did not see an influence; association between smoking habit and all endpoints of the BMCyt (except karyolytic cells) was evident; the basal MN frequency, in the majority of groups, follows those around the world; and the BMCyt was confirmed as a good health status biomarker. We emphasize the need for constant discussions on the parameters of cell death due to greater difficulty among the analyzers. [ABSTRACT FROM AUTHOR]