RESUMO
Brazil is one of the largest consumers of pesticides in the world. This high consumption has resulted in higher potential health risk to agricultural farm workers due to occupational exposure. Hence, the aim of this study is to evaluate genomic instability, using Buccal Micronucleus Cytome (BMCyt) and telomere length (TL) measurement as biomarkers of occupational exposure to pesticides in rural workers living in the State of São Paulo, Brazil. Genomic instability was evaluated in 81 pesticide-exposed farm workers (69 males and 12 females) with a mean age of 49.16 ± 10.06 years and a mean time job of 30.00 ± 14.00 years,81 non-exposed individuals (62 males and 15 females) with a mean age of 47.87 ± 10.66 years. BMCyt results showed significantly higher levels of cell damage (micronuclei and binucleated cells) and cell death (karyorrhectic and condensed chromatin cells) in subjects exposed to pesticide when compared to those non-exposed (p < 0.05). Although our results did not show significant differences in TL among exposed and non-exposed groups, effects in TL due to pesticide exposure was found in a multivariable linear regression model when we stratified the groups by age (≤ 49 years and ≥ 50 years old; ß = 11.21, p = 0.006). In addition, TL reduction on was identified in relation to an increase in cigarette pack consumption (ß = -0.633, p = 0.045). Furthermore, exposure to specific pesticides presented different effects in TL. Cypermethrin exposure resulted in a reduction in TL (ß = -18.039, p = 0.018), while abamectin exposure led to an increase in TL (ß = 23.990, p = 0.007). Thus, our findings substantiate genomic instability due to pesticides exposure.
Assuntos
Fazendeiros , Praguicidas , Adulto , Brasil , Dano ao DNA , Feminino , Instabilidade Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Praguicidas/toxicidade , Telômero/genéticaRESUMO
During the harvest period, tobacco workers are exposed to nicotine and it is known that absorption of the alkaloid via the leaves causes green tobacco sickness (GST). We investigated if GST and its symptoms are associated with DNA damage and alterations of the redox status. DNA damage was measured in lymphocytes of tobacco workers and controls (n = 40/group) in single cell gel electrophoresis assays. Exposure to nicotine was determined by plasma cotinine measurements, alterations of the redox status by quantification of the total antioxidant capacity (TEAC) and of thiobarbituric acid reactive substances (TBARS). The symptoms of GTS included nausea, abdominal cramps, headache, vomiting and dizziness, and 50% of the workers had more than one symptom. Cotinine levels were enhanced in the workers (111 ng/mL); furthermore, the extent of DNA damage was ca. 3-fold higher than in the controls. This effect was more pronounced in participants with GST compared to healthy nicotine exposed workers and increased in individuals with specific symptoms (range 22-36%). TBARS levels did not differ between workers and unexposed controls, while TEAC values were even increased (by 14.3%). Contact with nicotine present in tobacco leaves causes GTS and leads to damage of the DNA; this effect is more pronounced in workers with GTS symptoms and is associated with alterations of the redox status. Damage of the genetic material which was found in the workers may lead to adverse long-term effects that are caused by genomic instability such as cancer and accelerated ageing.
Assuntos
Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Dano ao DNA , Fazendeiros , Nicotiana/crescimento & desenvolvimento , Nicotina/toxicidade , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Adulto , Doenças dos Trabalhadores Agrícolas/genética , Doenças dos Trabalhadores Agrícolas/metabolismo , Brasil , Estudos de Casos e Controles , Cotinina/sangue , Feminino , Instabilidade Genômica/efeitos dos fármacos , Humanos , Masculino , Nicotina/metabolismo , Exposição Ocupacional/análise , Oxirredução , Estresse Oxidativo/genética , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Nicotiana/metabolismo , Adulto JovemRESUMO
OBJECTIVES: Lifestyle, obesity, and eating habits are emerging as determinants for the instability of telomeres. The increase in childhood and adolescent obesity and the association of biochemical profiles and dietary components with telomere length (TL) makes it an important issue in nutritional research. The aim of the present study was to investigate TL and its association with ethnic background, adiposity, clinical and biochemical parameters, and dietary patterns among Brazilian children and adolescents. METHODS: A cross-sectional study encompassing 981 children and adolescents between 7 and 17 y of age was performed. Dietary intake habits, anthropometry, and clinical data were collected. TL analysis was performed by quantitative polymerase chain reaction. RESULTS: Children presented significantly longer TL than adolescents (P = 0.046). Participants who self-declared as black, mulatto, or brown (P < 0.001) also showed longer TL than those who were white. Regarding biochemical parameters, individuals with altered glucose levels had shorter TL than normoglycemic participants in the total sample (P = 0.014). Such difference remained statistically significant in adolescents (P = 0.019). Participants who reported eating fruits and vegetables regularly had longer TL than those who did not (P < 0.001). CONCLUSION: The results suggested that both biochemical parameters and the intake of antioxidant-rich food, such as fruits and vegetables, are associated with the stability of telomere biology among young Brazilians.
Assuntos
Etnicidade/genética , Comportamento Alimentar/fisiologia , Obesidade Infantil/etnologia , Obesidade Infantil/genética , Homeostase do Telômero/genética , Adiposidade/genética , Adolescente , Antropometria , Brasil , Criança , Estudos Transversais , Dieta/efeitos adversos , Comportamento Alimentar/etnologia , Feminino , Humanos , Masculino , TelômeroRESUMO
Coal plants represent one of the main sources of environmental pollution due to the combustion process of this mineral and the consequent release of gases and particles which, in significant quantities, can lead to a potential risk to health and the environment. The susceptibility of individuals to the genotoxic effects of coal mining can be modulated by genetic variations in the xenobiotic detoxification and DNA repair processes. The aim of this study was to evaluate if xenobiotic metabolism polymorphism, base excision repair polymorphisms and non-homologous end joining repair polymorphism, could modify individual susceptibility to genomic instability and epigenetic alterations induced in workers by occupational exposure to coal. In this study, polymerase chain reaction was used to examine the polymorphic sites. The sample population comprising 70 coal mine workers and 71 workers non-exposed to coal. Our results demonstrated the effect of individual genotypes on different biomarkers evaluated. Significant decrease in % of global DNA methylation were observed in CYP1A1 Val/- exposed individuals compared to CYP1A1 Ile/Ile individuals. Coal workers who carried the XRCC4 Ile/Ile genotype showed decrease NBUD frequencies, while the XRCC4 Thr/- genotype was associated with decrease in Buccal micronucleus cells for the group not exposed. No influence of GSTM1 null, GSTT1 null, GSTP1 Ile105Val, hOGG1 Ser326Cys, XRCC1 Arg194Trp polymorphisms was observed. Thus, the current study reinforces the importance of considering the effect of metabolizing and repair variant genotypes on the individual susceptibility to incorporate DNA damage, as these processes act in a coordinated manner to determine the final response to coal exposure.
Assuntos
Minas de Carvão , Carvão Mineral/toxicidade , Dano ao DNA , Metilação de DNA , Exposição Ocupacional , Polimorfismo Genético , Homeostase do Telômero , Adolescente , Adulto , Idoso , Citocromo P-450 CYP1A1/genética , Reparo do DNA , Proteínas de Ligação a DNA/genética , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Xenobióticos/metabolismo , Adulto JovemRESUMO
Pesticides used at tobacco fields are associated with genomic instability, which is proposed to be sensitive to nutritional intake and may also induce epigenetic changes. We evaluated the effect of dietary intake and genetic susceptibility polymorphisms in MTHFR (rs1801133) and TERT (rs2736100) genes on genomic and epigenetic instability in tobacco farmers. Farmers, when compared to a nonexposed group, showed increased levels of different parameters of DNA damage (micronuclei, nucleoplasmic bridges, and nuclear buds), evaluated by cytokinesis-block micronucleus cytome assay. Telomere length (TL) measured by quantitative PCR was shorter in exposed individuals. Global DNA methylation was significantly decreased in tobacco farmers. The exposed group had lower dietary intake of fiber, but an increase in cholesterol; vitamins such as B6, B12, and C; ß-carotene; and α-retinol. Several trace and ultratrace elements were found higher in farmers than in nonfarmers. The MTHFR CT/TT genotype influenced nucleoplasmic bridges, nuclear buds, and TL in the exposed group, whereas TERT GT/TT only affected micronucleus frequency. We observed a positive correlation of TL and lipids and an inverse correlation of TL and fibers. The present data suggest an important role of dietary intake and subjects' genetic susceptibility to xenobiotics-induced damages and epigenetic alterations in tobacco farmers occupationally exposed to mixtures of pesticides.
Assuntos
Dieta , Predisposição Genética para Doença/genética , Instabilidade Genômica/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Praguicidas/efeitos adversos , Adulto , Brasil , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Fazendeiros , Feminino , Instabilidade Genômica/genética , Genótipo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Telomerase/genética , Encurtamento do Telômero/efeitos dos fármacos , NicotianaRESUMO
Tobacco farming has been proving to induce poor health outcomes in agricultural workers, genomic instability being the triggering one. This study evaluated influence of PON1 (paraoxonase 1), SOD2 (superoxide dismutase), OGG1 (8-oxoguanine glycosylase), XRCC1 (X-ray repair cross-complementing protein 1), and XRCC4 (X-ray repair cross-complementing protein 4) genes polymorphisms on DNA damage in 121 subjects occupationally exposed to pesticides mixtures and nicotine at tobacco fields and 121 non-exposed individuals. Inorganic elements (Cl, P, S and Zn) and cotinine levels were found increased in farmers, confirming exposure. Results show higher frequencies of buccal micronucleus (MN), nuclear buds (NBUD), binucleated cells (BN) and damage index (comet assay), reduced telomere length (TL), and increased parameters of oxidative stress in farmers compared to non-exposed individuals. PON1 Gln/Gln genotype was associated with increased MN frequency. SOD2 Val/Val showed association with increased frequency of MN and NBUD and decreased antioxidant activity. The XRCC1 Arg/Arg showed protective effect for MN, BN and TL, which was also positively influenced by OGG1 -/Cys. MN was decreased in XRCC4 -/Ile farmers. These genotypes also showed a risk for antioxidant activity. Our study proposes that PON1 and SOD2 variants play a role in xenobiotic-metabolizing system in farmers, while base excision repair (BER) pathway could be the repair mechanism involved in genomic instability suffered by tobacco farmers.
Assuntos
Arildialquilfosfatase/genética , Dano ao DNA , DNA Glicosilases/genética , Proteínas de Ligação a DNA/genética , Praguicidas/toxicidade , Superóxido Dismutase/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , Adulto , Ensaio Cometa , Fazendeiros , Feminino , Genótipo , Humanos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Polimorfismo Genético , NicotianaRESUMO
Tobacco farming is an important economic income in Brazil, although it has been challenged as regard the occupational exposure to both pesticides and nicotine endured by farmers. Chronic occupational exposure to complex mixtures can lead to health hazardous. We examined genomic instability and epigenetic changes in tobacco farmers occupationally exposed to pesticide mixtures and nicotine at tobacco fields. DNA damage was assessed by alkaline comet assay in blood cells. Genomic DNA was isolated, and telomere length was measured using quantitative polymerase chain reaction assay. We measured 5-methyl-2'-deoxycytidine, a marker of global DNA methylation, and p16 promoter methylation. The oxidative profile was evaluated by trolox equivalent antioxidant capacity and lipid peroxidation (thiobarbituric acid reactive substances) in serum. Exposure parameters, plasma cotinine and inorganic element levels, were also measured. DNA damage was significantly elevated for farmers in relation to unexposed group (P < 0.001; Mann-Whitney test) and positively associated with years of exposure. Inverse relationship between DNA damage and total equivalent antioxidant activity was demonstrated for exposed and unexposed groups. Exposed group showed significantly shorter telomeres (P < 0.001; unpaired t-test) and DNA hypomethylation (P < 0.001; unpaired t-test), as well as p16 hypermethylation (P = 0.003; Mann-Whitney test). Lipid peroxidation was increased for exposed group in relation to unexposed one (P = 0.02; Mann-Whitney test) and presented a positive correlation with global DNA methylation (P = 0.0264). Farmers have increased plasma cotinine levels (P < 0.001) and inorganic elements (phosphorus, sulphur and chlorine) in relation to unexposed group. Elevated oxidative stress levels due to chronic occupational pesticide mixtures and nicotine exposure in tobacco farmers were associated with higher DNA damage, shorter telomeres and altered DNA methylation. Telomere-accelerated attrition due to exposure may be potential intermediate step before a disease state.
Assuntos
Dano ao DNA/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Instabilidade Genômica/efeitos dos fármacos , Encurtamento do Telômero/efeitos dos fármacos , Adulto , Idoso , Brasil , Ensaio Cometa , Metilação de DNA/genética , Fazendeiros , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/toxicidade , Telômero/efeitos dos fármacos , Telômero/genética , Encurtamento do Telômero/genética , Nicotiana/toxicidadeRESUMO
BACKGROUND: Genetic damage may occur spontaneously under normal metabolic circumstances, inadequate intake of nutrients, and excessive exposure to environmental mutagens. OBJECTIVES: To evaluate the influence of the intake of micronutrients vitamin B12, vitamin B6, and folate and of the polymorphism methylenetetrahydrofolate reductase (MTHFR) C677T on the induction of DNA damage in tobacco farmers. METHODS: The study involved 66 men and 44 women engaged in tobacco cultivation in the region of Venâncio Aires (Rio Grande do Sul state, Brazil). Peripheral blood samples were collected to analyze DNA damage using the Comet assay, the micronucleus (MN) test and MTHFR C677T polymorphism. Dietary intake was evaluated based on the mean values obtained from three 24-h diet recall questionnaires, and nutrient intake data were computerized and estimated in the Food Processor SQL 10.9 program. The statistical tests used to generate the stated results were Kruskal-Wallis test, Exact Fisher's test, and multivariate linear regression analysis. RESULTS: DNA damage was significantly higher in individuals who had an inadequate intake of folate, vitamin B12, and vitamin B6 (P < 0.01) assessed by Comet assay. In relation to MN test results, buccal cells showed MN frequency higher in individuals with inadequate intake of vitamin B6 (P < 0.01). No difference was observed in MN lymphocytes frequency. No significant association was detected between MTHFR C677T polymorphism and DNA damage in tobacco farmers. CONCLUSION: Our results suggest that folate, vitamin B12, and vitamin B6 deficiency may be associated with genotoxic effect in individuals exposed to pesticides.
Assuntos
Dano ao DNA , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Micronutrientes/metabolismo , Exposição Ocupacional , Polimorfismo Genético , Complexo Vitamínico B/metabolismo , Adulto , Brasil , Fazendeiros/estatística & dados numéricos , Feminino , Ácido Fólico/metabolismo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Praguicidas/análise , Nicotiana , Vitamina B 12/metabolismo , Vitamina B 6/metabolismoRESUMO
Various pesticides in the form of mixtures must be used to keep tobacco crops pest-free. Recent studies have shown a link between occupational exposure to pesticides in tobacco crops and increased damage to the DNA, mononuclei, nuclear buds and binucleated cells in buccal cells as well as micronuclei in lymphocytes. Furthermore, pesticides used specifically for tobacco crops shorten telomere length (TL) significantly. However, the molecular mechanism of pesticide action on telomere length is not fully understood. Our study evaluated the interaction between a complex mixture of chemical compounds (tobacco cultivation pesticides plus nicotine) and proteins associated with maintaining TL, as well as the biological processes involved in this exposure by System Biology tools to provide insight regarding the influence of pesticide exposure on TL maintenance in tobacco farmers. Our analysis showed that one cluster was associated with TL proteins that act in bioprocesses such as (i) telomere maintenance via telomere lengthening; (ii) senescence; (iii) age-dependent telomere shortening; (iv) DNA repair (v) cellular response to stress and (vi) regulation of proteasome ubiquitin-dependent protein catabolic process. We also describe how pesticides and nicotine regulate telomere length. In addition, pesticides inhibit the ubiquitin proteasome system (UPS) and consequently increase proteins of the shelterin complex, avoiding the access of telomerase in telomere and, nicotine activates UPS mechanisms and promotes the degradation of human telomerase reverse transcriptase (hTERT), decreasing telomerase activity.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Fazendeiros , Nicotina/toxicidade , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Mapas de Interação de Proteínas , Encurtamento do Telômero/efeitos dos fármacos , Brasil , Humanos , Biologia de Sistemas , Telômero/efeitos dos fármacos , Telômero/metabolismo , Nicotiana/efeitos adversos , Nicotiana/química , Nicotiana/crescimento & desenvolvimentoRESUMO
Metal ions such as iron can induce DNA damage by inducing reactive oxygen species (ROS) and oxidative stress. Vitamin C is one of the most widely consumed antioxidants worldwide, present in many fruits and vegetables, especially inMalpighia glabra L., popularly known as acerola, native to Brazil. Acerola is considered a functional fruit due to its high antioxidant properties and phenolic contents, and therefore is consumed to prevent diseases or as adjuvant in treatment strategies. Here, the influence of ripe and unripe acerola juices on iron genotoxicity was analyzed in vivo using the comet assay and micronucleus test. The comet assay results showed that acerola juice exerted no genotoxic or antigenotoxic activity. Neither ripe nor unripe acerola juices were mutagenic to animals treated with juices, in micronucleus test. However, when compared to iron group, the pre-treatment with acerola juices exerted antimutagenic activity, decreasing significantly micronucleus mean values in bone marrow. Stage of ripeness did not influence the interaction of acerola compounds with DNA, and both ripe and unripe acerola juices exerted protective effect over DNA damage generated by iron.
RESUMO
Occupational exposure to pesticides in tobacco fields causes genetic damage in farmers. The aim of this study was to analyze tobacco farmers chronically exposed to low doses of pesticides and nicotine (present in the tobacco leaves) in relation to absolute telomere length (aTL), and explore the influence of lifestyle characteristics, oxidative stress, and inorganic element levels. DNA was isolated from peripheral blood samples from agricultural workers and non-exposed individuals, and aTL was measured by quantitative real time polymerase chain reaction (qPCR) analysis. Oxidative stress (thiobarbituric acid reactive substances [TBARS], which measures oxidative damage to lipids; and toxic equivalent antioxidant capacity [TEAC], which measures total equivalent antioxidant capacity) was evaluated in serum, and inorganic element content was analyzed in whole blood through particle-induced X-ray emission technique. It was found that exposure to pesticides and tobacco smoking had significant effects on aTL. Individuals occupationally exposed to complex mixtures of pesticides in tobacco fields and individuals who smoked had decreased aTL compared with the non-exposed group. TBARS and TEAC were significantly elevated in the exposed group. There were no significant differences in inorganic elements. There was no evidence of an influence of age, gender, consumption of alcoholic beverages, or intake of fruits and vegetables on aTL within the groups. In addition, years of work in the tobacco field in the exposed group did not influence any of the variables analyzed. Although further studies were needed, these results suggested differences in telomere maintenance in tobacco farmers compared with the control group, indicating that telomere length may be a good biomarker of occupational exposure.
Assuntos
Nicotiana/efeitos adversos , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Fumar/efeitos adversos , Telômero/efeitos dos fármacos , Adolescente , Adulto , Idoso , Brasil , Estudos de Casos e Controles , Dano ao DNA , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Fatores de Risco , Homeostase do Telômero/efeitos dos fármacos , Adulto JovemRESUMO
The abusive use of amfepramone in Brazilian population has grown in recent years. Few studies have been conducted on amphetamine with respect to DNA damage, and there have been no apparent investigations examining the influence of amfepramone on humans. The aim of this study was to determine the possible mutagenic actions of amfepramone on humans using the micronucleus (MN) assay with buccal cells and the effects of supplementation with vitamin C as a potential protective agent. The study included 108 females with 52 as control and 56 taking amfepramone at 120 mg/d for at least the whole previous month. All women were intentionally selected to be nonsmokers and nondrinkers. After 30 d of amfepramone women were given amfepramone plus vitamin C use at 1000 mg/d for another month. Results showed a marked increase in the number of MN in amfepramone users in both basal and differentiated cells, indicating a mutagenic action. After vitamin C supplementation, a significant decrease in the frequency of MN and apoptosis was observed. Evidence indicates that the main mechanism of action of amfepramone in inducing DNA damage occurs through formation of reactive oxygen species (ROS), intercalation and topoisomerase binding, attributed to the presence of an N-dialkyl group. In addition, data demonstrated that vitamin C effectively inhibited amfepramone-induced DNA damage.
Assuntos
Ácido Ascórbico/farmacologia , Suplementos Nutricionais , Dietilpropiona/toxicidade , Testes para Micronúcleos/métodos , Mutagênicos/toxicidade , Brasil , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Mucosa Bucal/citologia , Mucosa Bucal/efeitos dos fármacosRESUMO
Malpighia glabra L, popularly known as acerola, is considered a functional fruit and therefore is taken to prevent disease or as adjuvant to treatment strategies, since the fruit is an undeniable source of vitamin C, carotenoids, and flavonoids. Acerola is a natural source of vitamin C, flavonoids, and carotenoids. Its chemical composition is affected by genetic uniformity of the orchards and environmental factors. Considering the extensive growth of the culture of acerola in Brazil as well as its widespread use, this study evaluates the genotoxic and antigenotoxic activity of acerola in relation to geographical origin using the comet assay in mice blood cells in vitro. No acerola samples showed potential to induce DNA damage, independently of origin. Also, for antigenotoxicity activity, only the acerola sample from São Paulo reduced DNA damage induced by hydrogen peroxide (by about 56%). The sample from Ceará showed good antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl assay, in agreement with its higher rutin, quercetin, and vitamin C levels. Additional studies with other treatment regimens are necessary to better understand the impact of the complex mixture of acerola on genomic stability.
Assuntos
Dano ao DNA , Malpighiaceae/química , Extratos Vegetais/química , Animais , Ácido Ascórbico/análise , Compostos de Bifenilo , Brasil , Cromatografia Líquida de Alta Pressão , Ensaio Cometa , Sequestradores de Radicais Livres/química , Radicais Livres , Frutas/química , Geografia , Concentração Inibidora 50 , Masculino , Camundongos , Picratos , Quercetina/análise , Rutina/análiseRESUMO
Tobacco is a major Brazilian cash crop. Tobacco farmers apply large amounts of pesticides to control insect growth. Workers come into contact with green tobacco leaves during the tobacco harvest and absorb nicotine through the skin. In the present study, micronucleus frequency, cell death, and the frequency of basal cells were measured in tobacco farmers using the buccal micronucleus cytome assay (BMCyt), in parallel with measurement of blood butyrylcholinesterase (BChE) and nicotine levels. Polymorphisms in PONIGln192Arg and CYP2A6*9(-48T>G) were evaluated to verify the relationship between genetic susceptibility and the measured biomarkers. Peripheral blood and buccal cell samples were collected from 106 agricultural workers, at two different crop times (during pesticide application and leaf harvest), as well as 53 unexposed controls. BMCyt showed statistically significant increases in micronuclei, nuclear buds, and binucleated cells among exposed subjects in differentiated cells, and in micronuclei in basal cells. In addition, the exposed group showed higher values for condensed chromatin, karyorrhectic, pyknotic, and karyolitic cells, indicative of cell death, and an increase in the frequency of basal cells compared to the unexposed control group. A slight difference in mutagenicity using the BMCyt assay was found between the two different sampling times (pesticide application and leaf harvest), with higher micronucleus frequencies during pesticide application. Elevated cotinine levels were observed during the leaf harvest compared to the unexposed controls, while BChE level was similar among the farmers and controls. PONIGln192Arg and CYP2A6*9(-48T>G) polymorphisms were associated with DNA damage induced by pesticides and cell death.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Arildialquilfosfatase/genética , Dano ao DNA/efeitos dos fármacos , Nicotiana/toxicidade , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Polimorfismo Genético/genética , Agricultura , Brasil , Morte Celular/efeitos dos fármacos , Cotinina , Citocromo P-450 CYP2A6 , Marcadores Genéticos/genética , Humanos , Testes para Micronúcleos , Mucosa Bucal/citologia , Testes de Mutagenicidade , Nicotina/análise , Nicotina/toxicidade , Nicotiana/químicaRESUMO
Tobacco farming presents several hazards to those who cultivate and harvest the plant. The genotoxic and mutagenic effects in tobacco farmers were investigated. In order to verify the relationship between genetic susceptibility and biomarkers GSTT1, GSTM1, GSTP1, CYP2A6, PON, OGG1, RAD51, XRCC1, and XRCC4 genes polymorphism were evaluated. Oxidative stress markers and trace elements content were determined. Peripheral blood cells samples were collected from 111 agricultural workers during pesticides application and leaf harvest, and 56 non-exposed subjects. Results show that farmers are exposed to mixture of substances with genotoxic and cytotoxic potential. Only GSTM1 null and CYP2A6*9 showed significant associations with cytokinesis-blocked micronuclei assay results. In pesticide application an increase in trace elements content was observed. The results indicated that exposure to pesticides and nicotine can influence antioxidant enzymes activity. Our study drives the attention once more to the need for occupational training on safe work environment for farm workers.
Assuntos
Agricultura , Nicotiana , Nicotina/toxicidade , Exposição Ocupacional/análise , Praguicidas/toxicidade , Adulto , Hidrocarboneto de Aril Hidroxilases/genética , Biomarcadores/sangue , Catalase/sangue , Ensaio Cometa , Citocromo P-450 CYP2A6 , Feminino , Predisposição Genética para Doença , Glutationa Transferase/genética , Humanos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Polimorfismo Genético , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Nicotine has been reported to cause acute toxicity and to present long-term risks, such as chromosomal damage and genetic instability. The genotoxicity of nicotine may be mediated partly by an oxidative mechanism. We have evaluated the effects of the antioxidant vitamin C on nicotine-induced genotoxicity in mice. The comet assay and the micronucleus test were used to assess the effects of nicotine (15mg/kg) at different exposure times (2, 4, and 24h in the comet assay; 24h in the micronucleus test). Pretreatment with vitamin C 24h before nicotine exposure strongly protected mice against nicotine-induced DNA damage.
Assuntos
Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Nicotina/toxicidade , Animais , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Testes para Micronúcleos , Nicotina/antagonistas & inibidoresRESUMO
Genotoxic and antigenotoxic effects of acerola fruit at two stages of ripeness were investigated using mice blood cells. The results show that no ripeness stage of acerola extracts presented any genotoxic potential to damage DNA (Comet assay) or cytotoxicity (MTT assay). When antigenotoxic activity was analyzed, unripe fruit presented higher DNA protection than ripe fruit (red color) extract. The antioxidant capacity of substances also showed that unripe samples inhibit the free radical DPPH more significantly than the ripe ones. The results about determination of compounds made using HPLC showed that unripe acerola presents higher levels of vitamin C as compared to ripe acerola. Thus, vitamin C and the complex mixture of nutrients of Malpighia glabra L., and especially its ripeness stages, influenced the interaction of the fruit extract with the DNA. Acerola is usually consumed when ripe (red fruit), although it is the green fruit (unripe) that has higher potential as beneficial to DNA, protecting it against oxidative stress.
Assuntos
Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Malpighiaceae/química , Malpighiaceae/fisiologia , Extratos Vegetais/farmacologia , Animais , Antimutagênicos/farmacologia , Ácido Ascórbico/análise , Compostos de Bifenilo/metabolismo , Cromatografia Líquida de Alta Pressão , Ensaio Cometa , Testes Imunológicos de Citotoxicidade , Radicais Livres/metabolismo , Frutas/química , Frutas/fisiologia , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Picratos/metabolismoRESUMO
Amantadine (AMA) is an uncompetitive antagonist of the N-methyl-d-aspartate receptor, with clinical application, acting on treatment of influenza A virus and Parkinson's disease. It has been proposed that AMA can indirectly modulate dopaminergic transmission. In high doses, the central nervous system is its primary site of toxicity. To examine deleterious effects on CNS induced by AMA, this study evaluated possible neurobehavioral alterations induced by AMA such as stereotyped behavior, the effects on locomotion and memory and its possible genotoxic/mutagenic activities. Adult male CF-1 mice were treated with a systemic injection of AMA (15, 30 or 60 mg kg(-1) ) 20 min before behavioral tasks on open field and inhibitory avoidance. Higher AMA doses increased the latency to step-down inhibitory avoidance test in the training session in the inhibitory avoidance task. At 60 mg kg(-1) AMA induced impairing effects on locomotion and exploration and hence impaired habituation to a novel environment. Stereotyped behavior after each administration in a 3-day trial was observed, suggesting effects on dopaminergic system. Amantadine was not able to induce chromosomal mutagenesis or toxicity on bone marrow, as evaluated by the micronucleus assay. At the lowest dose tested, AMA did not induce DNA damage and it was unable to impair memory, locomotion, exploration or motivation in mice. However, higher AMA doses increased DNA damage in brain tissue, produced locomotor disturbances severe enough to preclude testing for learning and memory effects, and induced stereotypy, suggesting neurotoxicity.
Assuntos
Amantadina/toxicidade , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Dano ao DNA , Amantadina/farmacologia , Animais , Ensaio Cometa , Dopaminérgicos/toxicidade , Habituação Psicofisiológica/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos , Testes para Micronúcleos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Comportamento Estereotipado/efeitos dos fármacosRESUMO
Duloxetine is a potent inhibitor of serotonin and noradrenaline reuptake, with weak effects on dopamine reuptake, used in the treatment of major depression. It has been recognized that some antidepressants can affect memory in humans, but there is not study that report the duloxetine effect on memory using the inhibitory avoidance. The aim of this work was to investigate the effect of duloxetine on short- and long-term memory (STM and LTM) in the inhibitory avoidance task in mice. Duloxetine (10 and 20 mg/kg; i.p.) administered before or after the inhibitory avoidance training was not able to produce effects on STM e LTM (p>0.05). The group that received MK-801 (0.0625 mg/kg), an NMDA receptor antagonist, showed an impairment in STM and LTM (p<0.01). These effects were not reversed by duloxetine administration (p=0.114 and p=0.06, respectively). Duloxetine effect on memory 5 days after i.p. administration was also investigated. After this treatment both duloxetine doses used were unable to affect STM or LTM in the inhibitory avoidance task (p=0.371 and p=0.807, respectively). DNA damages were evaluated in brain tissues and blood by the comet assay, after subacute treatment (10 or 20 mg/kg by 5 days). Duloxetine did not induce genotoxic effects. However, when the cells were treated ex vivo hydrogen peroxide, a pro-oxidant effect on brain tissue from treated animals was observed with significantly higher DNA damage in comparison to untreated animals, suggesting increased susceptibility to injuries by reactive oxygen species in brain after treatment with duloxetine. Duloxetine did not produce any effect on memory after acute and subacute administration, suggesting that this antidepressant does not affect either memory acquisition or consolidation.