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1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 44(1): 18-23, 2010 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-20388358

RESUMO

OBJECTIVE: To explore the effect of 2,5-hexanedione (2,5-HD) on the levels of nerve growth factor (NGF) in sciatic nerve of rats and motor-neurons. METHOD: A total of 50 Wistar rats were randomly designed into five groups and intoxicated with 400 mgxkg(-1)xd(-1) 2,5-HD for 0, 7, 14, 21, 28 d. Immunohistochemistry and real-time PCR were used to detect the levels of NGF and NGF mRNA. Motor neuron VSC4.1 cells were administrated with 0, 2.5, 5.0, 10.0, 20.0 mmol/L 2,5-HD for 24 h and 10.0 mmol/L 2,5-HD was chosen to intoxicated VSC4.1 cells for 0, 1, 3, 6, 12, 24, 48 h respectively. Immunofluorescence technique was selected to detect the levels of NGF. RESULTS: The NGF level in sciatic nerve of rats administrated with 400 mgxkg(-1)xd(-1) 2,5-HD showed increase tendency at begin and then decrease after exposure. The NGF mRNA level in 14 d (2(-DeltaDeltaCt)= 3.46), 21 d (2(-DeltaDeltaCt)= 5.28) and 28 d (2(-DeltaDeltaCt)= 3.10) were higher than those in 0 d (2(-DeltaDeltaCt)= 1) and 7 d (2(-DeltaDeltaCt)= 0.78). In vitro tests of VSC4.1 cells showed that NGF levels in 5.0 mmol/L (43.24 +/- 7.52), 10.0 mmol/L (43.48 +/- 10.86) and 20.0 mmol/L (63.13 +/- 10.68) were higher than those in 0 mmol/L (16.32 +/- 4.20)(q values were 19.92, 19.72, 32.78, respectively, P < 0.01) and 2.5 mmol/L (19.78 +/- 2.66) (q values were 17.50, 17.42, 30.63, respectively, P < 0.01) in 24 h and the NGF level in 20.0 mmol/L was higher than those in 5.0 mmol/L (q = 13.04, P < 0.01) and 10.0 mmol/L (q = 11.71, P < 0.01). The NGF levels of VSC4.1 cells with 10.0 mmol/L 2,5-HD in 6 h (18.66 +/- 2.89), 12 h (23.14 +/- 6.08), 24 h (27.66 +/- 6.11) and 48 h (17.25 +/- 3.05) were increased compared with that in 0 h (10.18 +/- 1.81) (q values were 9.64, 15.74, 21.76, 8.50, respectively, P < 0.01), 1 h (9.31 +/- 1.28) (q values were 10.28, 16.17, 21.95, 9.20, respectively, P < 0.01) and 3 h (10.44 +/- 2.13) (q values were 9.25, 15.24, 21.17, 8.10, respectively, P < 0.01), and NGF levels in 12 h and 24 h increased compared with those in 6 h (q values were 5.24, 10.77, respectively, P < 0.01) and 48 h (q values were 7.31, 13.26, respectively, P < 0.01). CONCLUSION: 2,5-HD could increase NGF levels in sciatic nerve of rats and motor-neurons, and the dose or time dependent effects were observed in this study.


Assuntos
Hexanonas/toxicidade , Neurônios Motores/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Nervo Isquiático/efeitos dos fármacos , Animais , Linhagem Celular , Masculino , Neurônios Motores/metabolismo , Ratos , Ratos Wistar , Nervo Isquiático/metabolismo
2.
Artigo em Chinês | MEDLINE | ID: mdl-16737585

RESUMO

OBJECTIVE: To explore the mechanism of cytotoxic effect of 2, 5-hexanedione (2, 5-HD) on motor neuron. METHODS: Vsc4.1 (a cell line from motor neuron) was incubated with a series concentration of 2, 5-HD. The cell viability, Ca(2+) Mg(2+) ATPase and Na(+)K(+) ATPase were detected. Laser scanning confocal microscope (LSCM) was used for detecting intracellular calcium level. The average calcium level in VSC4.1 was measured by flow cytometry. RESULTS: The cell viability was decreased when Vsc4.1 cells were treated with 2, 5-HD at the dosage of 2.5, 5.0, 7.5, 10, 15 and 20 mmol/L for 24 hours. Compared with the control group the activity of Ca(2+) Mg(2+) ATPase was decreased to 70.02%, 77.44% and 47.47% respectively; the activity of Na(+)K(+) ATPase was decreased to 82.07%, 72.45% and 50.71%. The difference was significant. Intracellular free calcium of VSC4.1 cell was increased rapidly within 10 s and then recovered within 40 seconds when it was exposed to 33.5 mmol/L 2, 5-HD. An increase in intracellular calcium was observed when the VSC4.1 was treated with 33.5 mmol/L 2, 5-HD. The peak of intracellular calcium level occurred ten minutes later. CONCLUSION: The disturbance of calcium homeostasis may be involved in the mechanisms of neurotoxicity of 2, 5-HD.


Assuntos
Cálcio/metabolismo , Hexanonas/toxicidade , Neurônios Motores/metabolismo , Animais , ATPase de Ca(2+) e Mg(2+)/metabolismo , Linhagem Celular , Relação Dose-Resposta a Droga , Neurônios Motores/efeitos dos fármacos , Ratos , ATPase Trocadora de Sódio-Potássio/metabolismo
4.
Wei Sheng Yan Jiu ; 35(6): 675-7, 2006 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-17290738

RESUMO

OBJECTIVE: To investigate the association between polymorphisms of DNA repair gene XRCC1 and DNA damage in peripheral blood lymphocytes among workers exposed to formaldehyde. METHODS: One hundred and fifty-one workers exposed to formaldehyde from plywood factories and one hundred and twelve workers without occupational exposure to formaldehyde were recruited into this study. DNA damage levels were measured by comet assay. The polymorphisms of XRCC1 gene were analyzed by polymerase chain reaction(PCR) with restriction fragment length polymorphism(RFLP) method. The multiple covariance analysis was used to compare olive trail moment and comet trail length adjusted confounding factors. RESULTS: In formaldehyde exposed workers, after ages, smoking and drinking status and occupational exposure level were adjusted, means of Olive trail moment and comet trail length in the subjects with variant genotype at Arg280 His site (geometric means 4.30 and 13.42 respectively) were higher than subjects with wild type homozygote (geometric means 3.38 and 11.71 respectively), the differences were significant (Olive trail moment: P < 0.05, comet trail length: P < 0.01) . No associations between the polymorphisms at other three sites in XRCC1 gene and means of olive trail moment and comet trail length in exposure workers were found. CONCLUSION: The polymorphisms of XRCC1 gene may modulate the effects of DNA damages induced by formaldehyde in workers.


Assuntos
Dano ao DNA , Proteínas de Ligação a DNA/genética , Formaldeído/efeitos adversos , Exposição Ocupacional , Polimorfismo Genético , Adulto , Ensaio Cometa , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
5.
Zhonghua Yu Fang Yi Xue Za Zhi ; 39(6): 392-5, 2005 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-16329798

RESUMO

OBJECTIVE: To investigate the DNA and chromosome damage in peripheral blood lymphocyte of workers occupationally exposed to formaldehyde (FA). METHODS: All 151 workers occupationally exposed to FA from two plywood factories and 112 workers without occupational FA exposure working in a machine manufactory were recruited into this study. Comet assay and cytokinesis-block micronucleus technique was used to evaluate the DNA and chromosomal damage of peripheral blood lymphocyte. The air FA samples were collected with SKC 224-PCXR8 air samplers. Gas chromatography was used to analyze the FA level. Personal information including occupational history, age, sex, smoking and drinking status was collected by the questionnaire. RESULTS: The time weighted average concentration (TWA) of FA in the working environment of FA-exposed workers (range 0.10 - 7.88 mg/m(3)) was higher than those in controls (< 0.01 mg/m(3)). The olive tail moment (Olive TM) in low FA-exposed workers [3.03 (2.49 - 3.67)] was lower than that in high FA-exposed workers [3.95 (3.53 - 4.43)], but higher than that in controls [0.93 (0.78 - 1.10)], the differences were statistical significant (P < 0.05). Comet trail length in FA-exposed workers were significantly higher than that in controls [6.78 (6.05 - 7.60)], but no significant differences ware found between the high FA-exposed workers [12.59 (11.80 - 13.43)] and the low FA-exposed workers [11.25 (10.12 - 12.50)]. The frequency of micronuclei per 100 binucleated cells in low FA-exposed workers (0.41 +/- 0.25) was lower than that in high FA-exposed workers (0.65 +/- 0.36), but higher than that in controls (0.27 +/- 0.13), the differences were statistical significant (P < 0.05). The increased tendencies with the exposure levels were found in those three indices. In stratification analysis, the same results were found. CONCLUSION: In the current FA exposure levels, the DNA and chromosomal damage in peripheral blood lymphocyte might be induced by FA exposure, and be increased with the levels of exposure.


Assuntos
Dano ao DNA , Formaldeído/análise , Exposição Ocupacional/análise , Adulto , Consumo de Bebidas Alcoólicas , Ensaio Cometa , Formaldeído/intoxicação , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Testes para Micronúcleos , Fumar , Adulto Jovem
6.
Artigo em Chinês | MEDLINE | ID: mdl-16266506

RESUMO

OBJECTIVE: To study the delayed effect on neuropsychopathy and its related factors after acute organophosphorus pesticides poisoning (AOPP). METHODS: Two hundred and fifty-seven cases of AOPP in the observation period were chosen to follow-up 2 months later from the 4 county hospitals in Shandong Province where the incidence of organophosphorus pesticide poisoning is high. RESULTS: Nine cases of organophosphate induced delayed polyneuropathy (OPIDP) were found and the incidence rate was 3.5%. The occurrence of OPIDP were related to the need for emergent artificial respiration, and the degree of poisoning, and the kinds of organophosphorus pesticides (Ops). The positive rate of symptoms of peripheral nerves, central nerves and psychogeny except auditory and visual hallucination after poisoning was significantly higher than that before (P < 0.05). The patient's situation of health, economy and work became statistically worse (P < 0.05). CONCLUSION: We found some had delayed effects on neuropsychopathy after AOPP which could debase the patient's life quality. The control measure should be administered as early as possible.


Assuntos
Síndromes Neurotóxicas/etiologia , Intoxicação por Organofosfatos , Praguicidas/intoxicação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Zhonghua Yu Fang Yi Xue Za Zhi ; 39(3): 159-63, 2005 May.
Artigo em Chinês | MEDLINE | ID: mdl-15938843

RESUMO

OBJECTIVE: To investigate the association of XRCC1 polymorphisms and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers. METHODS: The study included 141 coke-oven workers who exposed to a high level of polycyclic aromahaplotpetic hydrocarbon and 66 non-exposed controls. Urinary 1-hydroxypyrene and chromosome damage in peripheral lymphocyte were measured. Four -tagging single nucleotide polymorphisms in XRCC1 gene, including C26304T, G27466A, G28152A and G36189A, were detected and the XRCC1 haplotypes were estimated by using an extension of Clark algorithm. The associations between haplotype pairs and micronuclei data were assessed by analysis of covariance in the exposed and non-exposed groups. RESULTS: The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 micromol/mol Cr respectively (P < 0.01). The cytokinesis-block micronucleus cytokinesis-block micronucleus frequencies (number of micronucleus per 1 000 binucleated lymphocytes) was significantly higher in coke-oven workers (0.95 +/- 0.66)% than in the controls (0.40 +/- 0.36)%, P < 0.01. The haplotype CGGG was associated with the decreased frequencies of total micronucleus, and the haplotypes TGGG (P = 0.01) and CGAG (P < 0.05) were associated with the increased frequencies of total micronucleus in the multivariate analysis with adjustment for covariates among coke-oven workers. CONCLUSIONS: The genetic polymorphisms of XRCC1 gene could influence the chromosome damage levels in coke-oven workers.


Assuntos
Quebra Cromossômica , Coque/intoxicação , Proteínas de Ligação a DNA/genética , Polimorfismo de Nucleotídeo Único , Adulto , China , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Linfócitos/metabolismo , Masculino , Testes para Micronúcleos/métodos , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Doenças Profissionais/genética , Doenças Profissionais/urina , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Pirenos/análise , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
9.
Zhonghua Yu Fang Yi Xue Za Zhi ; 39(3): 164-7, 2005 May.
Artigo em Chinês | MEDLINE | ID: mdl-15938845

RESUMO

OBJECTIVE: To investigate the association of polymorphisms of metabolic and DNA repair enzyme genes and DNA damage in peripheral blood lymphocytes in coke-oven workers. METHODS: One hundred and forty-four coke-oven workers and 50 controls were recruited in this study. Urinary 1-hydroxypyrene (1-OHP) levels were measured as the internal dose of polycyclic aromatic hydrocarbons exposure. DNA damage was detected by alkaline comet assay, and the value of 1.74 was used as the cut-off value to determine whether the individual's DNA damage was positive. The genotypes of CYP1A1, CYP2E1, GSTP1, NQO1, mEH and XRCC1 were determined by PCR-based methods. With adjustment for urinary 1-OHP, age, sex, multiple analysis of covariance was used to study the association between genotypes and the ln-transformed olive TM and multiple logistic regression was used to calculate the adjusted OR and the 95% CI for the risk of DNA damage. RESULTS: In 144 coke-oven workers, with adjustment for urinary 1-OHP, coking history and sex, the olive TM was significantly higher with XRCC1 280His allele than those with Arg allele (5.6 vs. 2.8, P < 0.01). The subjects with XRCC1 280His allele also have significantly higher risk for DNA damage than subjects with Arg allele (adjusted OR = 2.66, 95% CI = 1.00-7.14, P = 0.05) and the subjects with GSTP1 104Val allele have higher risk for DNA damage than subjects with Ile allele (adjusted OR = 1.90, 95% CI = 0.94-3.85, P = 0.07). CONCLUSION: XRCC1 and GSTP1 polymorphisms might influence the susceptibility of DNA damage in occupational PAH-exposed coke-oven workers.


Assuntos
Coque/intoxicação , Dano ao DNA , Enzimas Reparadoras do DNA/genética , Polimorfismo Genético , Adulto , Estudos de Casos e Controles , Ensaio Cometa , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , DNA Ligase Dependente de ATP , DNA Ligases/genética , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , NAD(P)H Desidrogenase (Quinona)/genética , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise
10.
Artigo em Chinês | MEDLINE | ID: mdl-15355699

RESUMO

OBJECTIVE: To investigate the associations of polymorphisms of metabolic enzyme genes with urinary 1-hydroxypyrene levels in coke oven workers. METHODS: One hundred and forty-eight workers from a coke oven plant and 69 controls without occupational PAHs exposure were selected in this study. Urinary 1-hydroxypyrene was detected by high performance liquid chromatography with florescence detector. The genotypes at I462V site in exon 7 of CYP1A1 gene, GSTM1, GSTT1, I105V site in GSTP1gene, Pst1 and Dra1 sites in CYP2E1 gene, P187S site in NQO1 gene, Kpn1, BamH1 and Taq1 sites in NAT2 gene, and H113Y, R139H sites in mEH gene were determined by PCR-based methods. Personal information including occupational exposure history, age, sex, smoking and drinking status was collected by the questionnaire. RESULTS: The level of urinary 1-hydroxypyrene in coke oven workers [(5.61 +/- 1.04) mol/mol Cr] was higher than that in control [(0.74 +/- 0.32) micro mol/mol Cr]. After adjusting external occupational exposure category and smoking, coke oven workers with variant homozygotes at H113Y site of mEH gene had significantly higher urinary 1-hydroxypyrene concentrations than those with heterozygotes, and wild homozygotes (6.41 +/- 1.09 vs. 6.24 +/- 1.08, and 4.62 +/- 0.95 micro mol/mol Cr, P < 0.05), and gene-gene interaction was found between CYP1A1 and mEH. CONCLUSION: Genetic polymorphism of mEH gene could be a susceptible biomarker in coke oven workers which was involved in the individual susceptibility on metabolism of PAHs.


Assuntos
Coque/efeitos adversos , Citocromo P-450 CYP1A1/genética , Epóxido Hidrolases/genética , Exposição Ocupacional , Pirenos/metabolismo , Dano ao DNA/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Humanos , Masculino , Hidrocarbonetos Policíclicos Aromáticos/intoxicação , Polimorfismo Genético , Pirenos/análise
11.
Artigo em Chinês | MEDLINE | ID: mdl-15355700

RESUMO

OBJECTIVE: To investigate the relationship between lymphocyte DNA damage and polycyclic aromatic hydrocarbons (PAHs) exposure in coke oven workers. METHODS: Two hundred and thirty-five coke oven workers and 30 controls were selected in this study. Alkaline single-cell gel electrophoresis was used to evaluate the lymphocyte DNA damage, HPLC was employed to measure 1-hydroxypyrene levels in spot urine samples which were obtained at the end of a workweek (4 days of 8 hours/day) and personal information including occupational exposure, age, sex, smoking and drinking status was collected by the questionnaire. RESULTS: The lymphocyte DNA damage level expressed as olive moment in coke oven workers was significantly higher than that of controls [2.47 (0.22 approximately 46.68) vs 0.94 (0.42 approximately 4.21), P < 0.01], and correlation between urinary 1-hydroxypyrene concentrations and olive moment was found (Spearman Partial correlation coefficient = 0.22, P < 0.01) in coke oven workers. The 1.9 of olive moment value was used as the limit to determine whether the subject DNA damage was positive. The coke oven workers had significantly higher risk in DNA damage (adjusted OR = 5.38, 95% CI = 2.07 approximately 14.08) than did controls, and dose-response relationships were also found between external exposure (exposure category) or internal doses (urinary 1-hydroxypyrene) and DNA damage. CONCLUSION: There are dose-effect and dose-response relationships between PAHs exposure and lymphocyte DNA damage in coke oven workers.


Assuntos
Coque/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos/intoxicação , Adulto , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfócitos/metabolismo , Masculino , Pirenos/análise , Pirenos/metabolismo , Inquéritos e Questionários
13.
Zhonghua Yu Fang Yi Xue Za Zhi ; 38(2): 94-8, 2004 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-15061915

RESUMO

OBJECTIVE: To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers. METHODS: One hundred and fourty-nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study. Urinary 1-hydroxypyrene levels were measured as the internal dose of PAH exposure. The 6 per 1 000 of micronucleus value was used as the cut-off value to determine whether the individual's chromosomal damage was positive. The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene-gene interaction. RESULTS: In 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2.01, 95% CI = 1.03 -3.91). Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR = 3.18, 95% CI = 1.18 - 8.62). The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR = 0.40, 95% CI = 0.19 - 0.88). No significant associations were found for other gene polymorphisms and chromosomal damage risk. In addition, the gene-gene interactions were also found among GSTM1, NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk. CONCLUSION: Significant associations between genetic polymorphisms in GSTM1, NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH-exposed workers, which related to the mechanism of PAH carcinogenesis.


Assuntos
Dano ao DNA/genética , Predisposição Genética para Doença/genética , Linfócitos/metabolismo , Exposição Ocupacional , Adulto , Epóxido Hidrolases/genética , Feminino , Glutationa Transferase/genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , NAD(P)H Desidrogenase (Quinona)/genética , Hidrocarbonetos Policíclicos Aromáticos/intoxicação , Polimorfismo Genético , Pirenos/análise , Fatores de Risco
14.
Artigo em Chinês | MEDLINE | ID: mdl-15033012

RESUMO

OBJECTIVE: To investigate DNA and chromosome damage in peripheral blood lymphocyte of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: One hundred and thirty-seven coke oven workers and 50 controls without occupational PAHs exposure were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate DNA and chromosomal damage levels in peripheral blood lymphocyte. Urinary 1-hydroxypyrene level was used to assess the personal internal PAHs exposure dose. Personal information including occupational history, age, sex, smoking and drinking status was collected by questionnaire. RESULTS: Urinary 1-hydroxypyrene level in coke oven workers [(5.76 +/- 1.04) micro mol/mol Cr] was significantly higher than that in controls [(0.70 +/- 0.32) micro mol/mol Cr]. The rate of CBMN and comet tail moment of lymphocyte in coke oven workers [8.0 per thousand (0.0 per thousand - 30.0 per thousand ) and 2.09 (0.31 - 75.41), respectively] were higher than those in controls [3.5 per thousand (0.0 per thousand - 13.0 per thousand ) and 1.05 (0.11 - 6.63), P < 0.05]. In controls, the comet moment in smokers was significantly higher than that in non-smokers [1.44 (0.23 - 6.63) vs 0.81 (0.11 - 3.47), P < 0.05]. According to the length of work, 137 coke oven workers were classified into 3 groups i.e. 0.5 yrs , 16.0 yrs and 22.0 yrs group, and the comet moments were 1.34 (0.31 - 37.84), 2.32 (0.49 - 52.97) and 3.20 (0.45 - 75.41) respectively after adjusting the age, sex, smoking, drinking and level of urinary 1-hydroxy-pyrene. There was a rising tendency along with the increase in length of work. CONCLUSION: Under present PAHs exposure levels, both comet assay and Cytokinesis-block micronucleus test could detect PAHs-induced genotoxicity in coke oven workers, and comet assay is more suitable to assess the cumulative damage effect on DNA.


Assuntos
Dano ao DNA , Linfócitos/metabolismo , Exposição Ocupacional/análise , Hidrocarbonetos Policíclicos Aromáticos/intoxicação , Adulto , Coque , Ensaio Cometa , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirenos/análise , Fatores de Tempo
15.
Biomed Environ Sci ; 17(4): 432-41, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15745248

RESUMO

OBJECTIVE: To define the differences in gene expression patterns between glycidyl methacrylate (GMA)-transformed human lung fibroblast cells (2BS cells) and controls. METHODS: The mRNA differential display polymerase chain reaction (DD-PCR) technique was used. cDNAs were synthesized by reverse transcription and amplified by PCR using 30 primer combinations. After being screened by dot blot analysis, differentially expressed cDNAs were cloned, sequenced and confirmed by Northern blot analysis. RESULTS: Eighteen differentially expressed cDNAs were cloned and sequenced, of which 17 were highly homologous to known genes (homology = 89%-100%) and one was an unknown gene. Northern blot analysis confirmed that eight genes encoding human zinc finger protein 217 (ZNF217), mixed-lineage kinase 3 (MLK-3), ribosomal protein (RP) L15, RPL41, RPS 16, TBX3, stanniocalcin 2 (STC2) and mouse ubiquitin conjugating enzyme (UBC), respectively, were up-regulated, and three genes including human transforming growth factor beta inducible gene (Betaig-h3), alpha-1,2-mannosidase 1A2 (MAN 1A2) gene and an unknown gene were down-regulated in the GMA-transformed cells. CONCLUSION: Analysis of the potential function of these genes suggest that they may be possibly linked to a variety of cellular processes such as transcription, signal transduction, protein synthesis and growth, and that their differential expression could contribute to the GMA-induced neoplastic transformation.


Assuntos
Carcinoma de Células Escamosas/patologia , Linhagem Celular Transformada , Compostos de Epóxi/toxicidade , Fibroblastos/efeitos dos fármacos , Pulmão/citologia , Metacrilatos/toxicidade , Poluentes Ocupacionais do Ar/toxicidade , Carcinoma de Células Escamosas/genética , Fibroblastos/citologia , Perfilação da Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Masculino , Manosidases/efeitos dos fármacos , Manosidases/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Ribossômicas/metabolismo , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Ubiquitinas/metabolismo , Dedos de Zinco/efeitos dos fármacos , Dedos de Zinco/fisiologia
16.
Zhonghua Yu Fang Yi Xue Za Zhi ; 37(5): 327-30, 2003 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-14680593

RESUMO

OBJECTIVE: To investigate the relationship between the urinary 1-hydroxypyrene level and cytokinesis-block micronucleus and the olive moment of comet assay in peripheral blood lymphocyte in coke oven workers. METHODS: One hundred and thirty-three workers from a coke plant and 28 referents without occupational PAH exposure were recruited in this study. Urinary level of 1-hydroxypyrene was measured by alkaline hydrolysis combined with high performance liquid chromatography as an internal exposure dose, and the DNA and chromosomal damage of peripheral blood lymphocyte were evaluated with comet assay and cytokinesis-block micronucleus method. Personal information including occupational history, age, sex, smoking and alcohol drinking, was collected by questionnaire. RESULTS: There existed a good correlationship between the urinary level of 1-hydroxypyrene and frequency of micronuclei per 1 000 binucleated cells or the olive moment of comet assay in the study subjects, after adjusting for sex, age, smoking and alcohol drinking (r > 0.25, P < 0.01). One hundred and sixty-one subjects were divided into three groups by their urine 1-hydroxypyrene level (expressed as 0.30 - 2.44, 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr), and the geometric means of their urinary levels of 1-hydroxypyrene were 1.14, 4.32 and 12.49 micro mol/mol Cr, respectively. After adjusting for age, sex, smoking and alcohol drinking by multiple nonparametric analysis of covariance, the median of olive moment of comet assay in the group of 7.10 - 33.10 micro mol/mol Cr was 3.67, significantly higher than that in the groups of 0.30 - 2.44 and 2.45 - 7.09; and the micronuclei frequencies in the groups of 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr were 8.00 per thousand and 7.50 per thousand, respectively, significantly higher than that in the group of 0.30 - 2.44 micro mol/mol Cr (6.00 per thousand ). CONCLUSIONS: The comet assay of peripheral blood lymphocyte was more suitable to detect the PAHs-induced early genotoxicity, than the cytokinesis-block micronucleus.


Assuntos
Coque/efeitos adversos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Pirenos/metabolismo , Adulto , Ensaio Cometa , Feminino , Humanos , Masculino , Testes para Micronúcleos
17.
Biomed Environ Sci ; 16(3): 283-94, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14631834

RESUMO

OBJECTIVE: To evaluate the genotoxic and nongenotoxic effects of short-term exposure to glycidyl mathacrylate (GMA) on human lung fibroblast cells (2BS cells) in vitro. METHODS: DNA strand breakage was determined by single cell gel electrophoresis, and DNA ladder formation assay and flow cytometric analysis were carried out to detect apoptic responses of cells to GMA exposure. The HPRT gene mutation assay was used to evaluate the mutagenicity, and the effect of GMA on gap junctional intercellular communication (GJIC) in the exposed cells was examined with the scrape loading/dye transfer technique. The ability of GMA to transform 2BS cells was also tested by an in vitro cell transformation assay. RESULTS: Exposure to GMA resulted in a dose-dependent increase in DNA strand breaks but not apoptic responses. GMA was also shown to significantly induce HPRT gene mutations and morphological transformation in 2BS cells in vitro. In contrast, GMA produced a concentration-dependent inhibition of GJIC. CONCLUSIONS: GMA elicits both genotoxic and nongenotoxic effects on 2BS cells in vitro. The induction of DNA damage and gene mutations and inhibition of GJIC by GMA may casually contribute to GMA-induced cell transformation.


Assuntos
Dano ao DNA , Compostos de Epóxi/toxicidade , Metacrilatos/toxicidade , Comunicação Celular , Diferenciação Celular , Ensaio Cometa , Análise Mutacional de DNA , Fibroblastos , Junções Comunicantes , Humanos , Hipoxantina Fosforribosiltransferase/genética , Pulmão/citologia
18.
Zhonghua Yu Fang Yi Xue Za Zhi ; 37(4): 259-62, 2003 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-12930676

RESUMO

OBJECTIVE: To explore the association of gene polymorphism of organophosphate insecticides (OPs) metabolic enzymes with intermediate myasthenia syndrome (IMS) following acute OPs poisoning. METHODS: Thirty six of 147 acute OPs poisoning patients developed IMS one to four days after poisoning. Peripheral blood samples were collected from all the patients and whole blood cholinesterase (ChE) activity was determined by DTNB spectrometry. The genetic polymorphism of CYP2E1 (1091C-->T) and GSTP1 (313A-->G) were analyzed by polymerase chain reaction (PCR)-restrict fragment length polymorphism, CYP1A1 (4889A-->G), GSTM1 and GSTT1 by allele-specific PCR, and PON1 at 55 codon (55L-->M) by PCR-single strand conformation polymorphism. RESULTS: The whole blood ChE activity in IMS patients was not significantly different from non-IMS patients at admission (38.22 +/- 17.56)% and (42.49 +/- 16.23)%, respectively, P > 0.05, but recovered much slower in IMS patients than that in non-IMS patients. The frequencies of heterozygote and variant homozygote of PON1 at 55 codon, GSTM1 null, and both GSTM1 and GSTT1 null were higher in IMS patients than those in non-IMS patients (P < 0.05), with odds ratios and their 95% confident intervals of 2.48 (1.06 - 5.78), 11.23 (2.95- 42.76), 2.53 (1.14 - 5.61) and 2.68 (1.20 - 5.97), respectively. CONCLUSIONS: Patients of OPs and its mixture poisoning with genotype of variant allele at 55 codon of PON1, GSTM1 null and both GSTM1 and GSTT1 null probably had higher risk for IMS.


Assuntos
Predisposição Genética para Doença , Inseticidas/intoxicação , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/genética , Compostos Organofosforados , Adulto , Colinesterases/metabolismo , Citocromo P-450 CYP2E1/genética , Feminino , Genótipo , Glutationa Transferase/genética , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Síndrome
19.
Zhonghua Nei Ke Za Zhi ; 42(12): 861-4, 2003 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-14728879

RESUMO

OBJECTIVE: We compared the characteristics of persons who had made multiple versus single suicide attempts to determine whether or not these are two independent subgroups and, thus, should be provided with different preventive services. METHODS: We administered a 2 - 3 hour interview that included a structured psychiatric examination to 325 individuals with suicide attempts who were treated at four city and county-level general hospitals. RESULTS: The age, gender, years of education, marital status, work status, and family economic status of the 52 persons who had made more than one suicide attempt were similar to those of the 273 persons who had made a single attempt. But repeaters were less likely than non-repeaters to live in rural villages and to attempt suicide by ingesting agricultural poisons. Moreover, repeaters considered suicide prior to the attempt for a longer time, had a lower quality of life in the prior month, had a stronger suicidal intent, had more chronic life events, had a higher chronic stress score, and were more likely to have mental illness (P's all < 0.05). CONCLUSIONS: Major differences in the characteristics of suicide attempters with and without a prior history of suicide attempts suggest that these are independent subgroups of attempters. These two types of attempted suicide require different preventive approaches.


Assuntos
Hospitais Gerais , Tentativa de Suicídio/prevenção & controle , Tentativa de Suicídio/psicologia , Adulto , China , Feminino , Humanos , Masculino , Qualidade de Vida , Sociologia , Inquéritos e Questionários
20.
Artigo em Chinês | MEDLINE | ID: mdl-14761484

RESUMO

OBJECTIVE: To explore the potential biochemical mechanisms of neuromuscular junction transmission (NMJT) dysfunction induced by organophosphorus insecticides. METHODS: Ten rats were dosed with phoxim (1,144 mg/kg) and 5 of them developed myasthenia. The NMJT function was evaluated by the mean consecutive differences (MCD) measured by stimulation single fiber electromyography (SSFEMG) with the frequency of stimuli at 20 Hz. The activity of Ca(2+)-ATPase, Na(+), K(+)-ATPase, cAMP dependent protein kinase (PKA), Ca(2+)/phospholipid dependent protein kinase (PKC), and tyrosine protein kinase (TPK) were determined. RESULTS: In comparison with the control and non-myasthenic rats, the results in myasthenic rats showed that: (1) the MCDs increased; (2) the activities of Ca(2+)-ATPase, Na(+), K(+)-ATPase and PKA decreased and were negatively correlated with MCD; (3) the activities of PKC and TPK increased, and were positively correlated with MCD; (4) the phosphorylation of serine residuals in sarcolemma was weaker and the phosphorylation of tyrosine residuals was stronger. CONCLUSIONS: The NMJT dysfunction is likely associated with the decrease in Ca(2+)-ATPase and Na(+), K(+)-ATPase activity. The acceleration of desensitization and prolongation of resensitization of nicotinic acetylcholine receptors occur following the increase in tyrosine phosphorylation and the decrease in serine phosphorylation induced by OPs poisoning.


Assuntos
Inseticidas/toxicidade , Miastenia Gravis/induzido quimicamente , Compostos Organotiofosforados/toxicidade , Animais , ATPases Transportadoras de Cálcio/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico , Eletromiografia/efeitos dos fármacos , Inseticidas/farmacocinética , Miastenia Gravis/enzimologia , Compostos Organotiofosforados/farmacocinética , Proteína Quinase C/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ratos
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