RESUMO
Alcohol use disorder (AUD) causes about 3.3 million deaths around the world each year. It is the primary risk factor for the global burden of diseases in American countries. Long-term abuse of alcohol induces numerous molecular and biochemical changes in tissues exposed to alcohol. The toxic effects of alcohol are mediated by DNA damage through various mechanisms, such as induction of oxidative damage, DNA adducts, crosslinks, and DNA strand breaks. The main aim of the current study was to compare the frequency of SNP polymorphisms in XRCC1 (rs7997782) and GSTP1 (rs1695) genes involved in DNA repair of single strand breaks (SSB) and xenobiotic detoxification between alcohol addicts and a control group comprised of non-drinkers. Genetic polymorphisms were identified following allelic specific PCR designed to generate the amplicons containing the variants. Then amplicons were sequenced, and sequences were aligned against the human genome reference deposited in GenBank using the CLC Sequence Viewer software (version 7.6.1). The GG homozygotes in rs1695 (GSTP1) were significantly (p = 0.023) 3.8x more frequent among those with AUD when compared to the control group. No SNP variation was observed in rs7997782 (XRCC1). rs1695 variant has been associated with susceptibility to various diseases, including those related to alcohol consumption.
Assuntos
Consumo de Bebidas Alcoólicas/genética , Reparo do DNA/genética , Eletroforese Capilar/métodos , Inativação Metabólica/genética , Polimorfismo Genético/genética , Adulto , Quebras de DNA de Cadeia Simples , Feminino , Glutationa S-Transferase pi/genética , Humanos , Masculino , Pessoa de Meia-Idade , Alinhamento de Sequência , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genéticaRESUMO
Electrochemical techniques were used to investigate the behavior of lomustine (CCNU) and its degradation in aqueous solution at a glassy carbon electrode (GCE). The in situ interaction of CCNU and chemically degraded CCNU (cdCCNU) with dsDNA was then investigated in dsDNA incubated solutions, using dsDNA electrochemical biosensors and comet assays. CCNU undergoes electrochemical reduction in two irreversible, diffusion-controlled, and pH-dependent redox processes, each with transfer of two electrons and one proton. At pHâ¯≥â¯10.1, the peak potential for the two processes was essentially pH-independent and involved only one electron. A mechanism was proposed for the reduction of CCNU in a neutral medium. In addition, it was found that CCNU underwent spontaneous degradation during incubation in aqueous solution, without the formation of electroactive degradation products. The degradation process was faster in basic media. Moreover, this pro-drug interacted with the DNA. Its metabolite(s) initially caused condensation of the double helix chains, followed by the unwinding of these chains. In addition, free guanine (Gua) was released from the dsDNA and oxidative damage to the DNA by the CCNU metabolite(s) was evidenced from the detection of 8-oxoGua and 2,8-oxoAde. These results were confirmed by the poly(dA)- and poly(dG)-polyhomonucleotide biosensors, which revealed the oxidative damage caused to both bases (guanine and adenine) of the dsDNA by the CCNU metabolite(s). The comet assay indicated breaks in the single strand DNA, complementing the results of the studies using differential pulse voltammetry. Conformational changes of dsDNA caused by CCNU and cdCCNU were confirmed using comet assays.
Assuntos
Antineoplásicos Alquilantes/farmacologia , Quebras de DNA de Cadeia Simples/efeitos dos fármacos , DNA/efeitos dos fármacos , Lomustina/farmacologia , Antineoplásicos Alquilantes/química , Técnicas Biossensoriais , DNA/química , Difusão , Estabilidade de Medicamentos , Técnicas Eletroquímicas , Eletrodos , Lomustina/química , Conformação de Ácido Nucleico/efeitos dos fármacos , ÁguaRESUMO
Photodynamic therapy (PDT) is an emerging clinical treatment currently being used against a wide range of both cancerous and noncancerous diseases. The search for new active photosensitizers as well as the development of novel selective delivery systems are the major challenges faced in the application of PDT. We investigated herein three chloroharmine derivatives (6-, 8- and 6,8-dichloroharmines) with quite promising intrinsic photochemical tunable properties and their ability to photoinduce DNA damage in order to elucidate the underlying photochemical mechanisms. Data revealed that the three compounds are quite efficient photosensitizers. The overall extent of photo-oxidative DNA damage induced by both 8-chloro-substituted ß-carbolines is higher than that induced by 6-chloro-harmine. The predominant type of lesion generated also depends on the position of the chlorine atom in the ß-carboline ring. Both 8-chloro-substituted ß-carbolines mostly oxidize purines via type I mechanism, whereas 6-chloro-harmine mainly behaves as a "clean" artificial photonuclease inducing single-strand breaks and site of base loss via proton transfer and concerted (HO--mediated) hydrolytic attack. The latter finding represents an exception to the general photosensitizing reactions and, to the best of our knowledge, this is the first time that this process is well documented. The controlled and selective production of different oxygen-independent lesions could be fine-tuned by simply changing the substituent groups in the ß-carboline ring. This could be a promising tool for the design and development of novel photo-therapeutic agents aimed to tackle hypoxic conditions shown in certain types of tumours.
Assuntos
Dano ao DNA/efeitos dos fármacos , Harmina/efeitos adversos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Antineoplásicos/farmacologia , Cloro , Quebras de DNA de Cadeia Simples , Harmina/análogos & derivados , Hidrólise , Isomerismo , OxirreduçãoRESUMO
Different studies have suggested an association between arsenic (As) exposure and damage to single-stranded DNA by reactive oxygen species derived from the biotransformation of arsenic. The single strand damages are converted to double strand damage upon interaction with ultraviolet radiation. Analysis of genomic integrity is important for assessing the genotoxicity caused by environmental pollutants. In this study, we compared the concentration of As in drinking water, nutritional status, lifestyle variables, and the level of genotoxicity in an exposed population and a control group. Arsenic content of water was determined using a portable Arsenator® kit. DNA fragmentation was determined using the two-tailed comet assay. Our results show that the exposed population had low nutritional consumption compared to the control group (P < 0.05). Furthermore, the water consumed by the exposed group had As concentration of 14.3 ± 8.4 mg/L, whereas the As level in the water consumed by the control group was 7.7 ± 3.5 mg/L. Analysis shows that the frequency of double strand break (DSB) fragmentation was higher in the population exposed to higher levels of As compared to that of the control group. These results suggest a possible association between the concentration of As in drinking water and lifestyle variables, with increasing fragmentation of DSBs in the exposed population.
Assuntos
Intoxicação por Arsênico/genética , Arsênio/toxicidade , Quebras de DNA de Cadeia Dupla , Quebras de DNA de Cadeia Simples , Água Potável/química , Adulto , Arsênio/análise , Intoxicação por Arsênico/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , MéxicoRESUMO
OBJECTIVE: To evaluate the expression of genes related to nuclear excision (ERCC8, XPA and XPC), homologous recombination and non-homologous end-joining (ATM, BRCA1, BRCA2 and LIG4) repair mechanisms, using quantitative PCR methodologies, and it relation with bone marrow cellularity in myelodysplastic syndrome (MDS). METHODS AND RESULTS: A total of 51 adult de novo patients with MDS (3 refractory anaemia (RA), 11 refractory anaemia with ringed sideroblasts (RARS), 28 refractory cytopenia with multilineage dysplasia (RCMD), 3 refractory anaemia with excess blasts type I (RAEB-I), 5 refractory anaemia with excess blasts type II (RAEB-II), and 1 chronic myelomonocytic leukaemia (CMML) were evaluated. For karyotype, 16.2% patients were defined as very low prognosis, 59.5% low risk, 8.1% intermediate risk, 5.4% high risk and 10.8% very high risk. For bone marrow cellularity, 17.6%, 17.6% and 64.7% presented as hypocellular, normocellular and hypercellular, respectively. Patients with hypocellular MDS had significantly decreased expression of ATM (p=0.000), BRCA1 (p=0.014), BRCA2 (p=0.003), LIG4 (p=0.004) and ERCC8 (p=0.000) than those with normocellular/hypercellular bone marrow, whereas XPA (p=0.049) and XPC (p=0.000) genes were increased. In patients with hypoplastic MDS, a low expression of ATM (p=0.0268), LIG4 (p=0.0199) and ERCC8 (p=0.0493) was significantly associated with the presence of chromosomal abnormalities. We detected positive correlations between BRCA1 and BRCA2 (r=0.416; p=0.007), ATM and LIG4 (r=0.472; p=0.001), LIG4 and BRCA1 (r=0.333; p=0.026), LIG4 and BRCA2 (r=0.334; p=0.025), ATM and XPA (r=0.377; p=0.008), ATM and XPC (r=0.287; p=0.046), LIG4 and XPC (r=0.371; p=0.007) and XPA and XPC genes (r=0.895; p=0.0000). We also found among all patients evaluated that correlation with LIG4 occurred most often. CONCLUSIONS: These correlations demonstrate the important intrinsic relations between single and double DNA strand breaks genes in MDS, emphasising that these genes are related to MDS pathogenesis.
Assuntos
Células da Medula Óssea/patologia , Enzimas Reparadoras do DNA/genética , Reparo do DNA , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Biópsia , Exame de Medula Óssea , Quebras de DNA de Cadeia Dupla , Quebras de DNA de Cadeia Simples , DNA Ligase Dependente de ATP/genética , Proteínas de Ligação a DNA/genética , Feminino , Regulação Enzimológica da Expressão Gênica , Marcadores Genéticos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição/genética , Proteína de Xeroderma Pigmentoso Grupo A/genética , Adulto JovemRESUMO
A modification of the original comet assay was developed for the simultaneous evaluation of DNA single strand breaks (SSBs) and double strand breaks (DSBs) in human spermatozoa. The two-dimensional perpendicular tail comet assay (2T-comet) combines non-denaturing and denaturant conditions to the same sperm nucleoid. In this case, the species-specific deproteinized sperm is first subjected to an electrophoretic field under non-denaturing conditions to mobilize isolated free discrete DNA fragments produced from DSBs; this is then followed by a second electrophoresis running perpendicular to the first one but under alkaline conditions to produce DNA denaturation, exposing SSBs on the same linear DNA chain or DNA fragments flanked by DSBs. This procedure results in a two dimensional comet tail emerging from the core where two types of original DNA affected molecule can be simultaneously discriminated. The 2T-comet is a fast, sensitive, and reliable procedure to distinguish between single and double strand DNA damage within the same cell. It is an innovative method for assessing sperm DNA integrity, which has important implications for human fertility and andrological pathology. This technique may be adapted to assess different DNA break types in other species and other cell types.
Assuntos
Ensaio Cometa/métodos , Quebras de DNA de Cadeia Dupla , Quebras de DNA de Cadeia Simples , Fragmentação do DNA , Humanos , Hibridização in Situ Fluorescente , Masculino , Microscopia de Fluorescência , EspermatozoidesRESUMO
Silica (SiO2) nanoparticles are being progressively applied in various applications, including cosmetics, food technology, and medical diagnostics. Although crystalline SiO2 is a known carcinogen, the carcinogenicity of SiO2 nanoparticles remains unclear. Here, we assessed the cytotoxic effects and DNA injury induced by exposure to various dosages of SiO2 nanoparticles at 0-2400 mg/mL (0-3200 mg/mL microscale SiO2 as positive control) for 24 h using RAW264.7 cells, followed by methyl tetrazolium (MTT) assay. Cells were also treated by 31.25, 125, and 500 mg/mL SiO2 nanoparticles (500 mg/mL microscale SiO2 as positive control) for 24 h and examined by single cell gel electrophoresis assay (SCEG) and flow cytometry. Outstanding dose-related decline in cell viability was observed with enhancing dosages of SiO2 nanoparticles by MTT assay. The inhibitory concentration 50% of SiO2 nanoparticles and microscale SiO2 was 16690 and 5080 mg/mL, respectively. The comet rate (comet%), length of tail, the percentage in DNA tail (TDNA%) and olive tail moment (OTM) induced by SiO2 nanoparticles were significantly increased in comparison with control and microscale SiO2 at 500 mg/mL. 500 mg/mL SiO2 nanoparticles and microscale SiO2 caused a significant increase in apoptosis rate, decreased proliferation index and increased cell proportions in G0/G1 phases by contrast to the negative control (P < 0.05). This indicates that SiO2 nanoparticles are more cytotoxic than microscale SiO2 particles; they induce DNA injury, increase apoptosis, and decrease the proliferation index in RAW264.7 cells. DNA injury and apoptosis may be involved in reducing cell proliferation.
Assuntos
Dano ao DNA , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Sobrevivência Celular/efeitos dos fármacos , Quebras de DNA de Cadeia Simples , Camundongos , Células RAW 264.7RESUMO
The ability of two 48 percent chlorpyrifos-based insecticides (Lorsban* 48E® and CPF Zamba®), two 50 percent pirimicarb-based insecticides (Aficida® and Patton Flow®), and two 48 percent glyphosate-based herbicides (Panzer® and Credit®) to induce DNA single-strand breaks in peripheral blood erythrocytes of Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae) exposed under laboratory conditions was evaluated by the single-cell gel electrophoresis (SCGE) assay. In those fish exposed to Lorsban* 48E®, CPF Zamba®, Aficida®, Patton Flow®, Credit®, and Panzer®, a significant increase of the genetic damage was observed for all formulations regardless of the harvesting time. This genotoxic effect was achieved by an enhancement of Type II-IV comets and a concomitant decrease of Type 0-I comets over control values. A regression analysis revealed that the damage varied as a negative function of the exposure time in those Lorsban* 48E®- and Aficida®-treated fish. On the other hand, a positive correlation between damage increase and exposure time was achieved after Patton Flow® and Credit® treatment. Finally, no correlation was observed between increase in the genetic damage and exposure time after treatment with CPF Zamba® or Panzer®. These results highlight that all agrochemicals inflict primary genotoxic damage at the DNA level at sublethal concentrations, regardless of the exposure time of the aquatic organisms under study, at least within a period of 96 h of treatment.
Assuntos
Carbamatos/toxicidade , Clorpirifos/toxicidade , Quebras de DNA de Cadeia Simples , Glicina/análogos & derivados , Herbicidas/toxicidade , Inseticidas/toxicidade , Poecilia/sangue , Pirimidinas/toxicidade , Animais , Bioensaio , Ensaio Cometa , Eritrócitos/efeitos dos fármacos , Eritrócitos/ultraestrutura , Glicina/toxicidade , Poecilia/genética , GlifosatoRESUMO
Cisplatin is currently used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication. It is a commonly used chemotherapeutic agent binding mono- or bifunctionally to guanines in DNA. Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain. The time required for both gene expression turn-off and return to normal weight DNA in wild-type E. coli was not accomplished even after 4 h post-treatment with cisplatin, while the same process takes place within 1.5 h after ultraviolet radiation (UV). Besides, a heavily damaging action of cisplatin can be seen not only by persistent nicks on genomic DNA, but also by NER gene expression exceeding manifold that seen after equivalent lethal doses of UV. Moreover, cisplatin caused an increase in uvrB gene expression from its putative upstream promoter P3 in an SOS-independent manner.
Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Quebras de DNA de Cadeia Simples , Escherichia coli/genética , Resposta SOS em Genética/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , DNA Bacteriano/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Mutação , Regiões Promotoras Genéticas , Transcrição Gênica , Raios Ultravioleta , Regulação para CimaRESUMO
A hospital-based unmatched case-control study was performed in order to determine the relation of DNA single (ssb) and double (dsb) strand breaks in women with and without cervical neoplasia. Cervical epithelial cells of 30 women: 10 with low grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 without cervical lesions were evaluated using alkaline and neutral comet assays. A significant increase in global DNA damage (ssb + dsb) and dsb was observed in patients with HG-SIL (48.90 ± 12.87 and 23.50 ± 13.91), patients with LG-SIL (33.60 ± 14.96 and 11.20 ± 5.71), and controls (21.70 ± 11.87 and 5.30 ± 5.38; resp.). Pearson correlation coefficient reveled a strong relation between the levels ssb and dsb (r(2) = 0.99, P = 0.03, and r(2) = 0.94, P = 0.16, resp.) and progression of neoplasia. The increase of dsb damage in patients with HG-SIL was confirmed by DNA breakage detection-FISH (DBD-FISH) on neutral comets. Our results argue in favor of a real genomic instability in women with cervical neoplasia, which was strengthened by our finding of a higher proportion of DNA dsb.
Assuntos
Ensaio Cometa/métodos , Quebras de DNA de Cadeia Dupla , Quebras de DNA de Cadeia Simples , DNA de Neoplasias/genética , Predisposição Genética para Doença/genética , Neoplasias do Colo do Útero/genética , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
There is an increased concern about the health effects that air-suspended particles have on human health which have been dissected in animal models. Using CD-1 mouse, we explore the effects that vanadium inhalation produce in different tissues and organs. Our findings support the systemic effects of air pollution. In this paper, we describe our findings in different organs in our conditions and contrast our results with the literature.
Assuntos
Poluição do Ar/efeitos adversos , Material Particulado/toxicidade , Vanádio/toxicidade , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Quebras de DNA de Cadeia Simples , Humanos , Sistema Imunitário/patologia , Inalação , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Camundongos , Modelos Animais , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/patologiaRESUMO
Sulfentrazone is an herbicide used as a pre-plant incorporated or pre-emergence treatment. The electrochemical oxidation of sulfentrazone was studied, by cyclic, differential and square-wave voltammetry on unmodified and on glassy carbon nanotube-modified electrodes, and by controlled-potential coulometry and electrolysis. The voltammograms of sulfentrazone showed a main irreversible diffusion-controlled pH-dependent oxidation peak. The in situ DNA-damaging capacity of sulfentrazone was also investigated, employing double stranded ds-DNA-modified glassy carbon electrode, without evidence of interaction. On the other hand, in a solution of sulfentrazone and single stranded ss-DNA, the oxidation signals of the respective bases decreased concentration-dependently, indicating binding of sulfentrazone to guanine and adenine. The electro-Fenton method was employed to promote decontamination by eliminating the herbicide, resulting in almost 60% of mineralization.
Assuntos
DNA de Cadeia Simples/efeitos dos fármacos , Herbicidas/química , Sulfonamidas/química , Triazóis/química , Quebras de DNA de Cadeia Simples , DNA de Cadeia Simples/química , Eletrólise , Herbicidas/toxicidade , Peróxido de Hidrogênio/química , Ferro/química , Sulfonamidas/toxicidade , Testes de Toxicidade/métodos , Triazóis/toxicidadeRESUMO
Paternal germline exposure to organophosphorous pesticides (OP) has been associated with reproductive failures and adverse effects in the offspring. Methyl-parathion (Me-Pa), a worldwide-used OP, has reproductive adverse effects and is genotoxic to sperm, possibly via oxidative damage. This study investigated the stages of spermatogenesis susceptible to be targeted by Me-Pa exposure that impact on spermatozoa function and their ability to fertilize. Male mice were exposed to Me-Pa (20 mg/kg bw, i.p.) and spermatozoa from epididymis-vas deferens were collected at 7 or 28 days post-treatment (dpt) to assess the effects on maturing spermatozoa and spermatocytes, respectively. Spermatozoa were examined for DNA damage by nick translation (NT-positive cells) and SCSA (%DFI), lipoperoxidation (LPO) by malondialdehyde production, sperm function by spontaneous- and induced-acrosome reactions (AR), mitochondrial membrane potential (MMP) by using the JC-1 fluorochrome, and fertilization ability by an in vitro assay and in vivo mating. Alterations on DNA integrity (%DFI and NT-positive cells) in spermatozoa collected at 7 and 28 dpt, and decreases in sperm quality and induced-AR were observed; reduced MMP and LPO were observed at 7 dpt only. Negative correlations between LPO and sperm alterations were found. Altered sperm functional parameters evaluated either in vitro or in vivo were associated with reduced fertilization rates at both times. These results show that Me-Pa exposure of maturing spermatozoa and spermatocytes affects many sperm functional parameters that result in a decreased fertilizing capacity. Oxidative stress seems to be a likely mechanism of the detrimental effects of Me-Pa exposure in male germ cells.
Assuntos
Reação Acrossômica/efeitos dos fármacos , Inseticidas/toxicidade , Metil Paration/toxicidade , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Quebras de DNA de Cadeia Simples/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Feminino , Fertilização/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Exposição Paterna , Distribuição Aleatória , Motilidade dos Espermatozoides/efeitos dos fármacos , Estatísticas não Paramétricas , Fatores de TempoRESUMO
The Monte Carlo (MC) method has been widely implemented in studies of radiation effects on human genetic material. Most of these works have used specific-purpose MC codes to simulate radiation transport in condensed media. PENELOPE is one of the general-purpose MC codes that has been used in many applications related to radiation dosimetry. Based on the fact that PENELOPE can carry out event-by-event coupled electron-photon transport simulations following these particles down to energies of the order of few tens of eV, we have decided to investigate the capacities of this code in the field of nanodosimetry. Single and double strand break probabilities due to the direct impact of gamma rays originated from Co60 and Cs137 isotopes and characteristic x-rays, from Al and C K-shells, have been determined by use of PENELOPE. Indirect damage has not been accounted for in this study. A human genetic material geometrical model has been developed, taking into account five organizational levels. In an article by Friedland et al. [Radiat. Environ. Biophys. 38, 39-47 (1999)], a specific-purpose MC code and a very sophisticated DNA geometrical model were used. We have chosen that work as a reference to compare our results. Single and double strand-break probabilities obtained here underestimate those reported by Friedland and co-workers by 20%-76% and 50%-60%, respectively. However, we obtain RBE values for Cs137, AlK and CK radiations in agreement with those reported in previous works [Radiat. Environ. Biophys. 38, 39-47 (1999)] and [Phys. Med. Biol. 53, 233-244 (2008)]. Some enhancements can be incorporated into the PENELOPE code to improve its results in the nanodosimetry field.
Assuntos
Método de Monte Carlo , Nanotecnologia , Radiometria/métodos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Quebras de DNA de Cadeia Simples/efeitos da radiação , Raios gama/efeitos adversos , Humanos , Probabilidade , Raios X/efeitos adversosRESUMO
Senna (Cassia angustifolia Vahl.) is widely used as a laxative, although potential side effects, such as toxicity and genotoxicity, have been reported. This study evaluated genotoxic and mutagenic effects of senna aqueous extract (SAE) by means of four experimental assays: inactivation of Escherichia coli cultures; bacterial growth inhibition; reverse mutation test (Mutoxitest) and DNA strand break analysis in plasmid DNA. Our results demonstrated that SAE produces single and double strand breaks in plasmid DNA in a cell free system. On the other hand, SAE was not cytotoxic or mutagenic to Escherichia coli strains tested. In effect, SAE was able to avoid H(2)O(2)-induced mutagenesis and toxicity in Escherichia coli IC203 (uvrA oxyR) and IC205 (uvrA mutM) strains, pointing to a new antioxidant/antimutagenic action of SAE.