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Objective@#New quantitative structure-activity relationship (QSAR) method was used to predict N-nitroso compounds (NOCs) carcinogenicity. This could provide evidences for health risk assessment of the chemicals.@*Methods@#Total 74 chemical substances of NOCs were included as target chemicals for this validation study by using QSAR Toolbox based on category approach and read-across. The included 74 NOCs were categorized and subcategorized respectively using "Organic functional groups, Norbert Haider " profiler and "DNA binding by OASIS V.1.1" profiler. Carcinogenicity of rat were used as target of prediction, the carcinogenicity@*results@#of analogues in chemical categories were cross-read to obtain the carcinogenic predictive results of the target chemicals. Results 74 NOCs included 26 nonclic N-nitrosamines, 24 cyclic N-nitrosamines and 24 N-nitrosamides The sensitivity, specificity and concordance of the category approach and read-across for predicting carcinogenicity of 74 NOCs were 75% (48/64), 70%(7/10) and 74% (55/74) respectively. The concordance for noncyclic N-nitrosamines, cyclic N-nitrosamines and N-nitrosamides were 88% (23/26), 71% (17/24) and 63% (15/24) respectively.@*Conclusion@#QSAR based on category approach and read-across is good for prediction of NOCs carcinogenicity, and can be used for high-throughput qualitative prediction of NOCs carcinogenicity.
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Objective: To investigate the mechanism of dinitrosopiperazine (DNP)-mediated heat-shock protein 70-2 (HSP70-2) expression involved in the metastasis of nasopharyngeal cancer (NPC). Methods: Non-cytotoxic concentration of DNP against NPC cell line 6-10B with low metastatic potential was determined by MTT assay. The expressions of HSP70-2 protein and mRNA in 6-10B cells treated with DNP (50 and 100 μmol/L) were detected by indirect immunofluorescence assay, Western blotting, and real-time fluorogenic quantitative-PCR, respectively. The expression of HSP70-2 was silenced by small interfering RNA (siRNA)-HSP70-2. The capabilities of invasion and migration of 6-10B cells treated with 100 μmol/L DNP were detected by Transwell assay. Results: The non-cytotoxic concentration of DNP against 6-10B cells was 0-100 μmol/L. After treatment with 100 μmol/L DNP, the expression of HSP70-2 was significantly increased and mainly located in the cytoplasm. This expression was also in a dose-dependent manner. The relative expression levels of HSP70-2 mRNA in 6-10B cells treated with 50 and 100 μmol/L DNP were 0.81 ± 0.14 and 0.81 ± 0.26, respectively, which were not significantly different from that of the blank control group (vs 1.04 ± 0.33, P > 0.05). The capabilities of invasion and migration in 6-10B cells were inhibited by silencing the expression of HSP70-2 induced by siRNA-HSP70-2. Conclusion: DNP can up-regulate the expression of HSP70-2 in 6-1 OB cells through post-transcriptional regulation mechanism and then mediate the metastasis of NPC cells. Copyright© 2014 by Tumor.
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As hipóteses sobre a associação entre fatores da dieta e tumores de cérebro relacionam-se aos compostos N-nitroso como favorecedores do desenvolvimento desses tumores e ao papel de antioxidantes dietéticos atuando como protetores, através da inibição da nitrosação dos precursores dos compostos N -nitroso. O objetivo deste artigo é identificar fatores da dieta associados aos tumores primários de cérebro em indivíduos adultos (??20 anos). Trata-se de um estudo caso-controle de base populacional, realizado na Região Metropolitana de Salvador, estado da Bahia, Brasil. Foram realizadas análises de regressão logística para a estimativa das razões de chances ajustadas e respectivos intervalos de confiança a 95 porcento. Os resultados apontam uma associação inversa para o maior consumo de laticínios (OR igual 0,32; 95 porcento IC: 0,13 ? 0,80) e vitamina C (OR igual 0,34; 95 porcento IC: 0,13 ? 0,88) para todos os tumores de cérebro agrupados. Para os tumores não-astrocíticos o maior consumo de refrigerantes (OR igual 0,20; 95 porcento IC: 0,06 ? 0,63) demonstrou efeito protetor. Conclui-se que os fatores da dieta podem atuar de forma diferente entre os tumores de cérebro; o efeito protetor das vitaminas antioxidantes, especialmente a vitamina C, sugere que o maior consumo de legumes e frutas pode diminuir o risco para o desenvolvimento desses tumores.
The hypotheses about the association between dietary factors and brain tumors are related to N-nitroso compounds as promoters of development of these tumors and the role of dietary antioxidants acting as guards, through the inhibition of nitrosation of precursors of N-nitroso compounds.The aim of this paper is to identify dietary factors associated with primary brain tumors in adults (??20 years). This is a population-based case-control study conducted in the metropolitan area of Salvador,Bahia, Brazil. Logistic regression estimated adjusted odds ratios and confidence intervals at 95percent. Theresults indicate an inverse association for the highest intake of dairy products (OR equal 0.32, 95 percent CI: 0.13 - 0.80) and vitamin C (OR equal 0.34, 95 percent CI: 0.13 to 0.88) for all grouped brain tumors. For nonastrocytic tumors, the highest consumption of soft drinks (OR equal 0.20, 95 percent CI: 0.06 to 0.63) demonstrated a protective effect. It was concluded that dietary factors may act differently among brain tumors; the protective effect of antioxidant vitamins, especially vitamin C, suggests that a higher consumption of vegetables and fruits can reduce the risk of developing these tumors.
Las hipótesis sobre la asociación entre factores dietéticos y los tumores cerebrales están relacionadas con los compuestos N-nitroso como promotores del desarrollo de estos tumores y el papel de los antioxidantes dietéticos en calidad de protectores, a través de la inhibición de la nitrosación de los precursores de compuestos N-nitroso. El objetivo de este artículo es identificar los factores de la dieta asociados a los tumores primarios de cerebro en individuos adultos (??20 años). Se trata de un estudio caso-control de base en la población, llevado a cabo en el área metropolitana de Salvador, Bahia, Brasil. Se analizaron análisis mediante regresión logística para estimar razones de posibilidades ajustadas y los respectivos intervalos de confianza al 95 por ciento. Los resultados indican una asociación inversa para el mayor consumo de productos lácteos (OR igual 0,32, IC 95 por ciento: 0,13 a 0,80) y vitamina C (OR igual 0,34, IC 95por ciento: 0,13 a 0,88) de todos los tumores cerebrales agrupados. Para los tumores no Astrocíticos, el mayor consumo de refrescos (OR igual 0,20, IC 95 por ciento: 0,06 a 0,63) demostró un efecto protector. Se concluyó que los factores dietéticos pueden actuar de forma diferente entre los tumores cerebrales; el efecto protector de las vitaminas antioxidantes, especialmente vitamina C, sugiere que um mayor consumo de legumbres y frutas puede disminuir el riesgo de desarrollar estos tumores.
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Humanos , Masculino , Femenino , Antioxidantes , Neoplasias Encefálicas , Dieta , Compuestos Nitrosos , Epidemiología Nutricional , Estudios de Casos y Controles , Recolección de Datos , Exposición a Riesgos Ambientales , Exposición ProfesionalRESUMEN
Objective To investigate the effect of nitrotyrosine (3-NT) on the expression of ?1D adrenoceptor (?1D-AR) mRNA in cultured vascular smooth muscle cells (SMCS) .Methods SMCS were obtained from the tunica media of thoracic aorta of 1 month old SD rats and cultured in DMEM medium. The experiment consisted of two parts. In part Ⅰ SMCS were incubated with 0,1, 10, 100 or 200 ?mol?L-1 3-NT for 24 h and in part Ⅱ SMCS were incubated with 100 ?mol?L-1 3-NT forO,12, 24, 48 or 72 h. The total RNA was isolated by using Trizol reagent. The expression of ?1D-AR mRNA was determined by RT-PCR and agarose gel electrophoresis. Results In part I incubation with 1 and 10 ?mol?L- 3-NT for 24 h had no significant effect on the expression of ?1D-AR mRNA while incubation with 100 or 200 ?mol?L-1 3-NT for 24 h decreased the expression of ?1D-AR mRNA compared with 0?mol?L-1 3-NT (P
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The mutagenicities of 40 kinds of soy sauce treated with 50 mmol/L nitrite, at pH 3.00, 1 h, 37℃ were detected on S. typhimurium TA 98 and TA 100. 38 kinds of soy sauce showed significant direct-acting mutagenicity toward 2 strains without S9 mix; and other 2 kinds presented indirect-acting mutagpnicity with S9 mix. The mutagenicities of retail soy sauce were markedly higher than that of the bottled, and 1 ml of samples of former induced more than 100 000 revertants of TA 100 without S9 mix. When No. 15 soy sauce was incubated with 1, 2, 3, 4, 5, 10 and 50 mmol/L nitrite, the equivalent of 1 ml of soy sauce induced 3384, 4452, 4823, 5400, 6792, 7536 and 10956 revertants, respectively, to TA 100 without S9 mix.
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Objective: To study the effect of grape procyanidin (GPC) on N-nitroso compounds-induced expression of TNF- mRNA and TGF-?1 mRNA in hepatic cells. Methods: NaNO2 was infused into Wistar rats by 50 mg/kg bw to induce mutation. GPC was infused by 100mg/kg bw and 10mg/kg bw respectively through mouth into the rats of two experimental groups. After 8 w situ hybridization was applied to measure the expression level of TNF-?mRNA and TGF-?1 mRNA in hepatic cells. Results: The expression rate of TNF-醡RNA and TGF-?1 mRNA of the hepatic cells in positive control group was 30.23 % and 19.47 % respectively, while that of high-dose GPC group was 11.94 % and 6.96 % respectively .The differences were statistically significant (P
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Crude catechins extracted from green tea had an ability of eliminating free radicals of active oxygen. The antioxidative activity of the catechins was 3.93 times higher than that of ascorbic acid. By adding 0.05% of the catechins to lard, the auto-oxidation induction phase of the lard was prolonged for 12 times, the peroxide value and the propanedialdehyde concentration were statistically lower at the level of P=0.01. In a model system of simulated stomach condition, the crude extract eliminated NaNO2 and inhibited the formation of N-nitroso compound's obviously, the elimination rate and the inhibition rate were 96.9% and 98.6%, respectively.Experiment in fowls showed that the extract could decrease the plasma total cholesterol and triglyceride
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The formation of carcinomas of liver, lung and kidney in rats by feeding aminopyrine (AP) plus sodium nitrite (Na NO2) in diet was investigated. 72 young Wister rats were divided into A,B,C,D group. Group A was set as control receiving basal diet and tap water. Another 3 groups were given basal diet containing AP plus Na NO2 (2g/kg each). However, group B was given tap water, group C ascorbic acid solution, group D sea buckthorn (Hippophae rhamnoides L.) juice for drinking. After 38 week's feeding, group B developed tumors in the livers (17/17), lungs (6/17) and kidneys (4/17) and the average life-span was 195 days, group D delayed the development of tumors and the average life-span was 270 days, significantly longer than that of group B (195 days, p
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Daily dietary intakes of nitrate, nitrite and vitamin C were investigated in Chanle county, Fujian province, where gastric cancer was very common, with a marked geographic variation in mortality. The average daily intake of nitrate of residents in Zhanggang village (high risk area) was 132.75 mg, which was significantly higher than that (84.65 mg) in Shouzhan village (moderate risk area), but similar to that (113.12 mg) in Meihua village (low risk area). However, nitrite intake in Zhanggang village was greatly higher than that in Shouzhan and Meihua villages (3.36 mg vs 0.21 and 0.37 mg, respectively). The average daily intake of vitamin C in Shouzhan village was 56.37 mg, significantly lower than that in Zhanggang village (123.09 mg) and in Meihua village (105.90 mg). The molar ratio of vitamin C intake to nitrite in the three villages was 3.22, 3.30 and 4.33, respectively. It was invesely associated with the mortality of gastric cancer. The results suggested that nitrate and nitrite might be etiological factors of gastric cancer in the county.
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The inhibiting effect of 11 kinds of ordinary vegetables including eggplant, cucumber, Chinese cabbage, fresh kidney bean, tomato, paprika, spinach, carrot, onion and celery on the formation of N-nitroso compounds was studied. Most vegetables inhibited the formation of N-nitrosodimethylamine when am-inopyrine and nitrite added to the vegetable juice and citric acid buffer were incubated in a model system simulated stomach condition (pH 3.00, T 37℃) for 1 hr. The inhibiting rate related to the contents of ascorbic acid in the vegetables ranged from 32.70% to 97.61%. Onion, fresh kidney bean, spinach and eggplant inhibited the formation of N-nitrosodimethylamine effectively with the inhibiting rate of 77.91%, 73.40%, 57.48% and 30.75% respectively (the inhibiting effect of ascorbic acid contained in the vegetables had been excluded). The relationship between the dose and the inhibiting effect of onion, fresn kidney bean, spinach and eggplant was good with the correlation coeffecient 0.756, 0.917, 0.607 and 0.801 (p