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Coke-oven workers are exposed to many kinds of pollutants that can cause health damage even lead to carcinogenesis. Therefore, it is critical to identify biomarkers that predict early health damage in these exposed individuals in molecular epidemiological studies. We applied an artificial neural network (ANN) model to the identification of such predictors in a study of coke-oven workers. The study included 330 steel-factory workers who were exposed to different levels of polycyclic aromatic hydrocarbons (PAHs) in the workplace and their levels of early health damage were determined by cytokinesis-block micronuclei (CMN), heat shock protein 70 (Hsp70) expression, benzo(a)pyrene diolepoxide-albumin adduct (BPDE-AA), and olive tail moment (OTM). The ANN model was built to predict the early health damage index, and the receiver operating characteristic (ROC) curve was used to illustrate the judged criteria and the ANN model. Trend Chi-square modeling was also performed. We found that there were 55 subjects with early health damage among 330 workers based on the multibiomarker criteria using the 95 percentile of the control group as the cut-off value, while there were 22-35 positive subjects if screening by any single biomarker. The Cochran-Armitage trend test for these findings were statistically significant (Z = 3.21, P = 0.0013). Six variables were selected to simulate the ANN model. The area under ROC (AUROC) was 0.726 ± 0.037 (P < 0.001), and the predictors included workplace, cholesterol, waistline, and others. Therefore, collective using CMN frequency, Hsp70 level, BPDE-AA level, and OTM with equal weights to make an initial screening test for early health damage in coke-oven workers is feasible and superior to any single biomarker. The determinants of the effects of multibiomarker on early health damage screening can be identified by the ANN model and ROC curve method.

Many studies have suggested that VSMC (vascular smooth muscle cell) apoptosis plays a key role in destabilization and rupture of atherosclerotic plaques. Therefore protection for VSMCs from apoptosis is a promising approach to stabilize 'vulnerable' lesions. However, the mechanisms as to why VSMCs in the fibrous cap often appear as profilerated in early stages, but turn apoptotic in advanced stages, are still unknown. In the present study, using RNAi (RNA interference) technology and a CaN (calcineurin) antagonist, the correlation between CaN and RANTES (regulated upon activation, normal T-cell expressed and secreted) in cultured rat apoptotic VSMCs stimulated by IFNgamma (interferon gamma; 20 ng/ml) and CD40L (CD40 ligand; 100 ng/ml) was investigated. RANTES released from VSMCs in each group was measured by ELISA and its mRNA in VSMCs was determined by RT (reverse transcription)-PCR. The total activity and expression of CaN in VSMCs were detected by the zymochemistry method and Western blot analysis respectively. From the results of the present study it can be hypothesized that an elevated CaN concentration in endochylema, by the CD40-CD40L signal pathway, induces VSMC apoptosis accomplished by the overexpression of RANTES. Therefore RANTES is a potential target for treating vulnerable atherosclerotic plaques owing to its crucial downstream regulating role in CaN-dependent VSMC apoptosis.

Plasma Free Amino Aoids in Workers Working under Different Stress Conditions: Tang-Chun Wu et al. Institute of Occupational Medicine, Tongji Medical University-Many harmful occupational factors induce the stress response and result in both the induction of heat stress proteins and the inhibition of the synthesis of other cellular proteins. Since amino acid levels are intimately linked to protein synthesis, we examined the free amino acid levels in the plasma of workers subjected to prolonged exposure to heat, carbon monoxide (CO) or both. The results showed that the levels of most amino acids tended to increase in the plasma of workers in stressful environments, and that free methionine and tryptophan increased significantly (p

To investigate the association of rs2910164 GC polymorphism and rs11614913 TC polymorphism in pre-miR-146a and pre-miR-196a2 with genetic damage levels in coke oven workers.A total of 575 nonsmoking workers who have worked for more than one year in a coke-oven plant at Wuhan, Hubei Province were enrolled in this study in September to October, 2010. The general characteristics as well as blood and urine samples were collected. The genetic damage levels were detected by cytokinesis-block micronucleus cytom assay and represented as micronucleus (MN) frequencies of binucleate cells in peripheral blood lymphocytes. The rs2910164 GC polymorphisms in pre-miR-146a and rs11614913 TC polymorphisms in pre-miR-196a2 were genotyped by using TaqMan assay. The plasma concentrations of benzo[a]pyrene-diolepoxide (BPDE)-albumin adducts were determined by using ELISA. All data were analyzed, the frequency ratio (FR) and 95%CI were calculated.Totally, 575 workers were taken into consideration. The rs2910164 C allele was associated with increased MN frequencies in the coke oven workers (P trend = 0.025), and the MN frequencies were higher in rs2910164 CC genotype carriers (4.38 ± 3.46) than in wild-type rs2910164 GG genotype carriers (4.02 ± 3.09) (FR = 1.18, 95%CI:1.04-1.34). The further stratified analyses by working years, gender, alcohol consumption, and the levels of BPDE-albumin adducts showed that the effects of rs2910164 C allele in increasing MN frequencies were robust in subjects who were males (FR = 1.11, 95%CI:1.02-1.20), nondrinkers (FR = 1.07, 95%CI:1.00-1.14), working years less than 20 (FR = 1.12, 95%CI:1.03-1.22), and workers with lower BPDE-albumin adducts levels (FR = 1.11, 95%CI:1.02-1.21) (P trend = 0.011, 0.044, 0.006 and 0.020, respectively). In addition, the MN frequencies were higher in workers with rs11614913 TC genotype (4.27 ± 2.91) than workers with rs11614913 TT genotype (3.90 ± 3.32) (FR = 1.12, 95%CI:1.02-1.23).Workers carried both rs2910164 GG and rs11614913 TT genotypes were set as a control, and the MN frequencies of workers with both rs2910164 CC and rs11614913 CC genotypes (5.32 ± 4.94) were 1.51 (1.21-1.89) times higher than the control (3.75 ± 3.01).The rs2910164 C allele in pre-miR-146a and rs11614913 C allele in pre-miR-196a2 were associated with increased genetic damage levels in coke oven workers.

Using the stable HSPA1A (HSP70-1) promoter-driven luciferase reporter HepG2 cells (HepG2/HSPA1A cells) to assess the overall toxicity of coke oven emissions.The stable HepG2/HSPA1A cells were treated with different concentrations of coke oven emissions (COEs) collected from the top, side, and bottom of a coke oven battery for 24 h. After the treatments, luciferase activity, cell viability, malondialdehyde (MDA) concentration, Olive tail moment, and micronuclei frequency were determined, respectively.The bottom COEs induced significant increases (P0.01) in relative luciferase activity up to 1.4 times the control level at 0.15 µg/L. The low dose of side COEs (0.02 µg/L) led to a significant increase (P0.01) in relative luciferase activity that progressively increased to 2.1 times the control level at 65.4 µg/L. The top COEs produced a strong dose-dependent induction of relative luciferase activity up to over 5 times the control level at the highest concentration tested (202 µg/L). In HepG2/HSPA1A cells treated with the bottom COEs, relative luciferase activity was positively correlated with MDA concentration (r = 0.404, P0.05). For the three COEs samples, positive correlations were observed between relative luciferase activity and Olive tail moment and micronuclei frequency.The relative luciferase activity in HepG2/HSPA1A cells can sensitively reflect the overall toxicity of COEs. The stable HepG2/HSPA1A cells can be used for rapid screening of the overall toxicity of complex air pollutants in the workplace.

To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and lung function in coke oven workers, and to provide scientific basis for further exploring the potential mechanism and developing the preventing strategies of the workers' early lung damage.We measured carbon monoxide, sulfur dioxide, benzene soluble matter, particulate matters, and PAHs at different workplaces of a coke oven plant. Detailed information on demography and occupational health condition of 912 workers were collected. We divided these workers into control group and coke oven group according to their workplaces and the different concentrations of COEs in the environment. We detected 10 urinary PAH metabolites and lung function using gas chromatography-mass spectrometry and spirometric tests, respectively.FEV(1.0) (91.12 ± 13.31) and FEV(1.0)/FVC (108.61 ± 20.37) of the coke oven group is significantly lower than the control group (94.16 ± 15.57, 113.45 ± 19.70). In the coke oven group, the hydroxyphenanthrene and 1-hydroxypyrene are negatively correlated with FEV(1.0)/FVC (β = -0.136, β = -0.100), Ptrend0.05 for all.The dose response decrease of lung function is associated with the urinary PAH metabolites in coke oven workers. Indicated that the long exposure to PAHs may cause the early lung damage in coke oven workers, phenanthrene and pyrene may be the main factors.

To explore the effects of smoking on urinary 10 metabolites of polycyclic aromatic hydrocarbons (PAHs) in the coke oven workers.Occupational health examination was performed on 1401 coke oven workers in one coking plant, their urine were collected respectively. The concentrations of the ten monohydroxy polycyclic aromatic hydrocarbons in urine were detected by gas chromatography/mass spectrometry. The 1401 workers were divided into four groups, namely control, adjunct workplaces, bottom and side, top group according to their workplaces and the different concentrations of PAHs in the environment. The concentrations of the ten monohydroxy polycyclic aromatic hydrocarbons between smokers and nonsmokers in each workplace group were compared using analysis of covariance, respectively.The levels of concentrations of the sixteen polycyclic aromatic hydrocarbons we detected at control were significantly higher than those at other areas (P0.05). Comparing the ten monohydroxy polycyclic aromatic hydrocarbons levels between smokers and nonsmokers, the levels of 1-hydroxynaphthalene and 2-hydroxynaphthalene among smokers were higher than nonsmokers with statistically significance in control, adjunct workplaces, bottom and side and top groups (P0.05). However, the levels of 1-hydroxypyrene had no statistically significant differences between the four areas.Urinary 1-hydroxynaphthalene and 2-hydroxynaphthalene may be used as biomarkers for the impact of smoking on monohydroxy polycyclic aromatic hydrocarbons in the coke oven workers.

To investigate the effects of occupational exposure to formaldehyde on the micronuclei frequencies in peripheral blood lymphocytes of workers.Two hundred thirty six plywood workers were divided into 3 exposure groups (low, middle and high) according to internal exposure biomarker (formaldehyde human serum albumin conjugate, FA-HSA), which was detected by ELISA. The concentrations of formaldehyde (FA) in air of two workshops were measure using the high performance liquid chromatography. Cytokinesis-block micronucleus (CBMN) test was used to detect the micronuclei frequencies of peripheral blood lymphocyte in 236 workers.The average concentrations of FA in the low and high exposure workshops were 0.58 +/- 0.20 and 1.48 +/- 0.61 mg/m3, respectively, there was significant difference (P0.01). The average concentrations of serum FA-HAS of workers in two workshops were 69.22 +/- 15.37 and 136.29 +/- 89.49 pg/ml, respectively, there was significant difference (P0.01). The results of CBMN test showed that the micronucleus frequencies in low, middle and high exposure groups were 1.94 +/- 1.72, 2.10 +/- 1.92 and 2.10 +/- 1.70 per thousand, respectively, there were no significant differences between groups. However, the micronucleus frequencies in accumulative low, middle and high exposure groups were 1.36 +/- 1.36, 2.31 +/- 1.81 and 2.49 +/- 1.92 per thousand, respectively, there were significant differences between different accumulative exposure groups (P0.01). The results of correlation analysis indicated that there was a positive correlation between accumulative exposure levels and micronucleus frequencies (r(s) = 0.321, P0.01). The accumulative exposure doses may be a risk factor for high micronucleus frequencies in workers exposed to FA (P(trend) = 0.002).FA-HSA levels can serve as an internal exposure biomarker for assessing the exposure level of workers exposed to FA. Accumulative formaldehyde exposure resulted in an increase of micronuclei frequencies of peripheral blood lymphocyte in plywood workers.

To investigate the relevance between single nucleotide polymorphisms (SNPs) in CHRNA3-CHRNB4-CHRNA5 gene cluster and DNA damage levels in the coke oven workers.A total of 309 male subjects from a steel plant in Northern China were divided into high exposure group (154 workers) and low exposure group (155 workers) according to the concentrations of plasma benzoapyrene-r-7, t-8, t-9, c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts. DNA damage levels of peripheral blood lymphocytes were examined by comet assay. Allelic discrimination of SNPs in CHRNA3-CHRNB4-CHRNA5 gene cluster were detected using Matrix-assisted laser desorption/ionization mass spectrometry.The Olive tail moment (OTM) (1.23 ± 1.05) of peripheral blood lymphocytes in the high exposure group was significantly higher than that (0.80 ± 1.07) in the low exposure group (P0.01). In the high exposure group, OTM (1.64 ± 0.17) of subjects with rs667282CC genotype was significantly higher than those (0.95 ± 0.13 or 1.09 ± 0.11) of subjects with rs667282CT genotype or rs667282TT + CT genotype (P0.01); OTM (1.60 ± 0.17) of subjects with GG genotype at rs12910984 site was significantly higher than those (0.92 ± 0.13 or 1.07 ± 0.10) of subjects with AG genotype or AG + AA genotype (P0.01); OTM (1.35 ± 0.17 or 1.64 ± 0.17) of the TA/TA or CG/CG diplotype carriers was significantly higher than that (0.89 ± 0.13) of TA/CG diplotype carriers (P0.05). However, the relevance between genotypes of these SNPs and the DNA damage levels was not found in the low exposure group.The rs667282CC genotype and rs12910984GG genotype on CHRNA3-CHRNB4-CHRNA5 gene cluster are associated with increased DNA damage levels in the high PAHs exposure group.

Previous investigations indicate that cooks are exposed to polycyclic aromatic hydrocarbons (PAH) from cooking oil fumes (COF). However, Emission of PAH and their carcinogenic potencies from cooking oil fumes sources have not been investigated among cooks.To investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), in different groups of cooks and different exposure groups, and to study the association between 8-OHdG and 1-hydroxypyrene (1-OHP), a biological marker for PAH exposure.Urine samples were collected from different groups of cooks (n = 86) and from unexposed controls (n = 36), all are male with similar age and smoking habits. The health status, occupational history, smoking, and alcohol consumption 24 hours prior to sampling was estimated from questionnaires. The urinary samples were frozen for later analyses of 8-OHdG and 1-OHP by high performance liquid chromatography.Excretion in urine of 8-OHdG were similar for controls (mean 1.2 µmol/mol creatinine, n = 36), and for those who had been in the kitchen room with exhaust hood operation (mean 1.5 µmol/mol creatinine, n = 45). COF exposed cooks without exhaust hood operation had increased excretion of 8-OHdG (mean 2.3 µmol/mol creatinine, n = 18). The difference between this group and the unexposed controls was significant. The urinary levels of ln 1-OHP and ln 8-OHdG were still significantly correlated in a multiple regression analysis.Results indicate that exposure to PAH or possibly other compounds in COF may cause oxidative DNA damage.

To investigate the association of -689C/T polymorphism in the peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) promoter with myocardial infarction (MI).This is a case-control study, which included 194 subjects with MI and 693 subjects without MI in nondiabetic Han population in Wuhan. Polymerase chain reaction-restriction fragment length polymorphism was used to determine the -689C--T substitution.The CC,CT, and TT genotype frequencies of -689C/T polymorphism were 88.1%,11.9%,and 0.0 in MI patients and 93.1%,6.6%,and 0.3% in controls, respectively (CC vs. CT+TT, P=0.025). The -689T allele was an independent risk factor for MI (OR=2.125, 95%CI: 1.206-3.744, P=0.009) after adjusting for age,sex,waist circumference,body mass index, smoking, alcohol drinking, physical activities, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, level. The -689T allele carriers had significantly higher TC levels than noncarriers [(5.05+/-1.16) mmol/L vs. (4.78+/-1.05) mmol/L, P=0.004] in the total population.The PPARgamma2 promoter -689C/T polymorphism is associated with an increased risk of MI.

To investigate the relationship between excision repair cross complementation group 4 ERCC4 gene polymorphisms and DNA damage in lymphocytes of coke oven workers and controls.Two hundred and forty-six coke oven workers and one hundred and twenty-seven controls were recruited in the study, and peripheral vein blood was drawn after over night fasting. Comet assay was used to evaluate DNA damage, and TaqMan-MGB probes were used to analyze ERCC4 genetic variations including the three Tagged-single nucleotide polymorphisms (Tag SNPs), referred to rs744154, rs3136079 and rs31870 which were picked out from Hapmap database. Then haplotypes were reconstructed by PHASE2.0.2 software.The lymphocytes Olive TM value of coke oven workers was significantly higher than that of controls (1.26+/-1.12 vs 0.52+/-0.97, P0.01). Among coke oven workers, no significant difference was found between the Olive TM of those with different genotypes or haplotype pairs at ERCC4 gene (P0.05). However, in the control group, the TG genotype carriers had higher Olive TM than the TT and GG genotype carriers (0.26+/-0.96 vs 0.66+/-0.98 and 0.66+/-0.51, P0.05), and the CTG/CTG haplotype pairs carriers had the highest Olive TM (0.69+/-1.01), and no CTG haplotype carriers had the lowest Olive TM (0.25+/-0.80), and the difference was borderline (P=0.08).The gene polymorphism at ERCC4 gene has no effects on the DNA damage of lymphocytes in coke oven workers, but the TG genotype carriers has lower DNA damage in the control. DNA damage is influenced by the interaction of genetic and environmental factors.

To investigate the relationship between heat shock protein 72 (Hsp72) and DNA genetic damage in peripheral blood lymphocytes of coke oven workers and the role of Hsp72 in protection of cells from genetic damage induced by coke oven emissions.Two hundred and sixty-seven coke oven workers and thirty controls without occupational PAHs exposure were investigated. Benzo[a]pyrene concentrations in the ambient air individually collected were assayed by high performance liquid chromatography (HPLC). Western Blot was used to measure Hsp72 levels and Comet assay was used to evaluate DNA damage degree. Personal information was collected by questionnaire.The Hsp72 level (G+/-S(G)) and olive comet tail moment (G+/-S(G) of peripheral blood lymphocytes in high-exposure workers (1.24 +/- 0.42 and 4.49 +/- 1.24) were significantly higher than those in low-exposure workers (1.01 +/- 0.35 and 2.99 +/- 1.10, P0.05) and control (0.85 +/- 0.34 and 2.40 +/- 1.00, P0.05) respectively. The Hsp72 median level of all subjects was used as the limit to divide subjects into high Hsp72 level group and low Hsp72 level group. The rate with high Hsp72 level was 36.7%, 43.1% and 58.3% in control, low exposure and high exposure workers respectively and had a rising tendency following exposure level (P = 0.003). In high Hsp72 level group Hsp72 level in high exposure workers was significantly higher than that in control (P0.05), and there was a rising tendency along with the increase of exposed levels. But the olive comet tail moment had no significant difference among three exposed groups (P0.05). In low Hsp72 level group there no difference among three exposed groups about Hsp72 levels. The olive comet tail moment in high exposure workers was significantly higher than that in low exposure workers and control (P0.01) and high exposure workers in Hsp72 positive group and there was a rising tendency along with the increase of exposed levels. Hsp72 levels had strong negative correlation with the olive comet tail moment (r = -0.503, P0.01) in high exposure workers.The coke oven emissions can induce hsp72 expression. Hsp72 play a role of protecting cells from DNA damage induced by coke oven emissions.

To investigate the application of BPDE-albumin adducts as monitoring biomarkers for coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs) and to explore possible relationship between BPDE-albumin adducts and urinary 1-hydroxypyrene (1-OHP) levels in them.Thirty-seven coke oven workers from a coke plant and 47 controls without the occupational exposure to PAHs were recruited in this study. The levels of plasma BPDE-albumin adducts and urinary 1-OHP were analyzed using high performance liquid chromatography.The median levels of BPDE-albumin adducts (42.10 fmol/mg albumin) and urinary 1-OHP (5.46 micromol/mol creatinine) were significantly higher in coke oven workers than in controls (14.16 fmol/mg albumin, 2.96 micromol/mol creatinine, respectively; P0.01). Multiple logistic regression analysis showed that coke oven workers were at higher risk of having BPDE-albumin adduct levels above 25.30 micromol/mg albumin (OR=1.79, P0.01) and urinary 1-OHP levels above 4.13 micromol/mol creatinine (OR=2.45, P0.05). There was a positive correlation between the levels of BPDE-albumin adducts and urinary 1-OHP in all subjects (rs=0.349, P0.01).BPDE-albumin adduct is a useful biomarker for monitoring long-term exposure to PAHs, and plasma BPDE-albumin adducts level is significantly correlated to urinary 1-OHP levels in coke oven workers.

To assess the expression of Hsp72 and Hsp73 in chronic obstructive pulmonary disease (COPD) and to evaluate their roles in damage from coal dust exposure.A case control study of 50 coal miners suffering from COPD and 50 healthy coal miners were selected from one coal mine. The levels of Hsp72 and Hsp73 in peripheral blood lymphocytes were determined by flow cytometry for all subjects.(1) The expression of basic Hsp72 of peripheral blood lymphocytes for patients and controls was not different from that inducible expressed Hsp72 by 42 degrees C heat stress or by BPDE exposure. (2) The expression of Hsp72 in COPD patients (17.7 +/- 4.9) was significantly lower than that in healthy coal miners (22.6 +/- 10.0) (P0.01). On the other hand, the expression of Hsp73 in COPD patients (33.5 +/- 11.7) was higher than that in healthy coal miners (19.6 +/- 5.9) (P0.01). (3) A-positive relationship between the expression of Hsp72 and cumulative inhaling coal dust exposure was observed. No relationship was found between Hsp73 and cumulative inhaling coal dust exposure.The decreased expressions of Hsp72 in peripheral blood lymphocytes of COPD coal miners.

To identify the single nucleotide polymorphisms (SNPs) in the regulatory and coding regions of heat shock protein 60 gene and search for its genetic makers in Chinese Han people.The 5' flank region, parts of the exons and introns of hsp60 gene were resequenced to identify the SNPs in Chinese Han people, and then the sequenced results to the Japanese, European and African's data in National Center for Biotechnology Information (NCBI) and HapMap databases were compared.One novel SNP was identified in exon 2 resulting in synonymous variant and the G allele frequency was 0.025. There were 11 reported SNPs in the sequenced region. The minor allele frequencies of rs1116734, rs3749095, rs1050347, rs8539 were 0.51, 0.30, 0.29, 0.49. The heterozygosity of the other 7 SNPs was 0. The distributions of rs1116734, rs1050347, rs8539, rs3749095 in Chinese Han people were similar to the Japanese's. The hsp60 rs3749095 which was not found in Japanese people was a high-frequency SNP in Chinese Han people; the distribution of rs8539 in Chinese Han people was quite different from European and African's (P0.01).The SNPs of hsp60 in Chinese Han people are different from the other peoples. The SNPs of hsp60 gene rs1116734, rs3749095, rs1050347, rs8539 are very common in Chinese Han people and might be used for candidate genetic markers of hsp60 gene.

The proliferation and metastasis of cancers depend on angiogenesis. This property provides the feasibility for the treatment of cancer by inhibition of angiogenesis, and many angiogenic inhibitors have been demonstrated to effectively inhibit angiogenesis and consequently the growth of solid cancer. As for the newly identified angiogenesis inhibitor, arresten, some studies have found its high activity on restrainting tumor vessel. This study was to assess the anti-angiogenic activity of arresten.The arresten gene was obtained from a healthy puerperal's placenta tissue by the reverse transcriptase-polymerase chain reaction (RT-PCR) method, and molecular cloning to prokaryotic expression plasmid pBV220 by recombination strategy. The prokaryotic expression plasmid pBV220/arr was identified by restriction enzyme digestion and sequenced. The pBV220/arr was transformed into E. coli JM109, DH5alpha, BL21 and BL21 (DE3) by the CaCl2 transformation method. The arresten expression level was detected by SDS-PAGE. The expressed product was purified, re-naturalized and detected for its biological activity of inhibiting the angiogenesis of chorioallantoic membrane (CAM).The arresten gene was cloned and pBV220/arr was constructed. The arresten expression level of protein was highly increased after pBV220/arr was transformed into E. coli BL21 (DE3). SDS-PAGE showed that the expressed arresten proteins were mainly inclusion bodies and had a molecular weight of 26 kDa. The expressed arresten protein showed evident biological activities.The successful construction of recombinant plasmid pBV220/arr and the effective expression in E.coli have laid a foundation for further study of its anti-angiogenic function and may pave the way for future anti-tumor application.

To explore the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, T1 and susceptibility to mountain sickness.Forty-three soldiers with acute mountain sickness and 80 healthy soldiers matching with sex/age and training under the same condition were divided into case group and control group. A multiple polymerase chain reaction method was used to detect GSTM1 and GSTT1 genes in genomic DNA isolated from peripheral blood cells from both cases and controls.The frequency of the GSTT1 positive genotype was significantly higher in cases (69.8%) than in controls (42.5%) (P = 0.004, OR = 3.12, 95% CI 1.42 approximately 6.86). The frequency of GSTM1 negative genotype was also higher in cases (72.1%) than in controls (52.5%) (P = 0.03, OR = 2.34, 95% CI 1.05 approximately 5.02). Persons with both GSTM1 and GSTT1 negative genotypes had 5-fold more risk than those with GSTT1 negative and GSTM1 positive genotypes in developing mountain sickness (OR = 5.04, 95% CI: 1.00 approximately 25.3).Genetic polymorphisms of glutathione S-transferase M1, T1 may be the risk factors in the development of mountain sickness.

To study the influence of occupational exposure and smoking on lung ventilation function of coke oven workers.Environmental monitoring was performed on the top, side and bottom of some coke ovens. Lung ventilation function test was performed in 234 coke oven workers.The poison concentration in environment had such tendency as it was the highest on the top, then the side, and the lowest at the bottom. The standardized forced expiratory volume in the 1st second (FEV(1), 90.8% +/- 8.6%) and forced expiratory rate (FEV(1)%, 95.4% +/- 12.4%) of those coke oven workers who smoked were significantly lower than those non-smoking workers (100.9% +/- 14.3%, 108.9% +/- 17.6%); among those smoking workers, the partial correlation coefficients between forced vital capacity (FVC) and benzene soluble, benzopyrene, and smoking index were -0.249, -0.187 and -0.368 respectively; and the coefficients between FEV(1) and the three aspects were -0.255, -0.191 and -0.388; and the coefficients between FEV(1)% and them were -0.131, -0.107 and -0.065. Among those non-smoking workers, the coefficients between benzene solubles and FVC, FEV(1) and FEV(1)% were -0.154, -0.052 and -0.176, and between benzopyrene and them were -0.121, -0.037 and -0.159.The lung ventilation function of coke oven workers has certain negative correlation with both occupational exposure and smoking.

To investigate the relationship between heat stress proteins 70 (HSPs70) gene polymorphism and the risk of acute mountain sickness.Fifty-six soldiers with acute mountain sickness and 173 soldiers without that were chosen as cases and controls. HSP70-1, HSP70-2 genotypes were analyzed by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.The HSP70-1 polymorphism was similar in two groups. The genotype frequency of HSP70-2 B/B in acute mountain sickness group (23.2%) was significantly higher than that in the control (6.9%, P0.05, OR = 4.02).There is a significantly increased association of HSP70-2 B/B genotype with the risk of acute mountain sickness. Individuals with HSP70-2 B/B genotype may have weaker adaptive ability than those without this genotype under altitude stress. The results contribute to provide scientific bases for finding these individuals in specified occupational people, ensuring their health and enhancing work efficiency.

To study the levels of nitric oxide synthase (NOS) and nitric oxide (NO) in patients with coronary heart disease (CHD), and the factors affecting them.Concentrations of NO and the activities of NOS in plasma in 136 patients and 206 controls using the corresponding Kits were measured. The data were analyzed using covariance and multiple linear regression analysis with SAS 8.1.The levels of NO [(217.05 +/- 153.31) micromol/L] and NOS [(14.09 +/- 7.14) U/ml] in patients were significantly higher than that in the healthy controls [(140.69 +/- 90.96) micromol/L, (7.75 +/- 3.79) U/ml, respectively, P0.01]. Smoking and drinking were the independent risk factors for NOS, while sex was the independent risk factor for NO (P0.01).The levels of plasma NO and NOS are closely related with coronary heart disease.

To study the pattern of polymorphism expression of heat-shock protein 70 (HSP70) family in A549 cell line treated with different concentrations of benzo(a)pyrene (BaP) and its probable biological effect.Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) was used for the HSP70 expression analysis.2D-PAGE showed that when A549 cells were exposed to different concentrations of BaP (0.1, 1.0, 5.0, 10.0 micromol/L) for 24, 48 h respectively, the HSP72 in A549 gradually declined as BaP concentrations increased [the integral OD (IOD)] for 24 h were: 150.36 +/- 26.03, 98.57 +/- 13.34, 64.92 +/- 15.03, 34.65 +/- 19.10, 32.92 +/- 18.71 respectively, for 48 h: 126.85 +/- 17.41, 106.19 +/- 15.32, 73.64 +/- 21.02, 35.18 +/- 11.95, 16.27 +/- 9.35 respectively), while the IOD of HSP73 did not show any remarkable change (24 h: 102.29 +/- 21.24, 87.71 +/- 18.70, 71.19 +/- 14.08, 71.87 +/- 15.16, 72.78 +/- 17.31 respectively; 48 h: 86.66 +/- 16.86, 75.67 +/- 10.61, 66.83 +/- 12.63, 67.29 +/- 10.26, 91.37 +/- 13.68 respectively).BaP can inhibit HSP72 expression and with certain dose-effect relationship, but cannot affect HSP73 expression.

Benzo[a]pyrene (B[a]P), a ubiquitous environmental pollutant, is a potent procarcinogen and mutagen that can elicit tumors, leading to malignancy. Heat shock proteins (Hsp) have been shown to protect cells against damages caused by various stresses including exposure to numerous chemicals. Whether Hsps, or more specifically Hsp70, are involved in repair of B[a]P-induced DNA damage is currently unknown.We assessed the potential role of the inducible form of Hsp70 in B[a]P-induced DNA damage of human embryonic lung (HEL) cells using immunoblot and the comet assay (i.e., the single cell gel electrophoresis assay).Exposure to B[a]P induced a dose-dependent decrease in the level of Hsp70, but a dose-dependent +-increase in DNA damage both in untreated (control) HEL cells and in cells preconditioned by a heat treatment. Heat preconditioning prior to B[a]P exposure potentiated the effect of B[a]P at a low dose (10 micromol/L), but appeared to be protective at higher doses. There was a negative correlation between Hsp70 level and DNA damage in the non-preheated as well as in the preconditioned cells.These data suggest that exposure of HEL cells to B[a]P may induce a dose-dependent reduction in the levels of the inducible Hsp70. The detailed mechanisms for the reduction of Hsp70 levels by B[a]P and the role of Hsp70 in DNA damage under different concentrations of B[a]P remains to be determined.

To explore heat shock protein 70 (HSP70) expression of A549 cells and its role in DNA damage caused by benzo(a)pyrene (BaP).Human adenocarcinoma A549 cells were cultured in vitro, exposed by different concentrations of BaP (0, 1.25, 2.50, 5.00, 10.00 micro mol/L) for 6 hours, or 10 micro mol/L of BaP for different time (0, 4, 8, 12, 16, 24 and 48 h). Then HSP70 expression and DNA damage were detected using Western-blot and single cell gel electrophoresis (SCGE) assay respectively, and the relationship between HSP70 expression and DNA damage was further analyzed.The integral optical densities of HSP70 in A549 cells treated with 1.25, 2.50, 5.00 and 10.00 micro mol/L BaP for 6 h (49.63 +/- 1.30, 45.72 +/- 1.03, 40.53 +/- 0.95, 37.50 +/- 1.20 respectively) were lower than that of the control cells (59.43 +/- 1.17) (P0.05). When A549 cells were exposed to 10 micro mol/L BaP for 4, 8, 12, 16 h, the integral optical densities of HSP70 were 33.33 +/- 0.80, 29.23 +/- 0.91, 12.51 +/- 0.96, 9.50 +/- 1.25 respectively, and there was an increasing tendency of the expression of HSP70 for 24 - 48 h (20.06 +/- 1.38, 24.51 +/- 1.39), however, all were different from that in control group (56.59 +/- 0.85) (P0.05). DNA damage scores in 10(6) A549 cells treated with 2.50, 5.00 and 10.00 micro mol/L BaP for 6 h (23,718 +/- 2,938, 30,128 +/- 2,937, 44,231 +/- 3,846) were significantly higher than that of the control cell (9,615 +/- 1,923) (P0.05). When A549 cells were exposed to 10 micro mol/L BaP for 4, 8, 12, 16, 24, 48 h, DNA damage scores (16,667 +/- 4,003, 38,461 +/- 1,924, 5,615 +/- 3,847, 76,282 +/- 2,937, 7,513 +/- 1,110 and 58,975 +/- 9,487) were also higher than that of control group (P0.05). There was a negative correlation between DNA damage and the expression of HSP70 when A549 cells were exposed to different concentrations of BaP.HSP70 might enhance intracellular defenses against DNA damage induced by BaP.

To explore the biomarkers of early diagnosis in patients with polycyclic aromatic hydrocarbons (PAHs)-related lung cancer for the application to detection of occupational lung cancer or related lung cancer.Western dot blotting was used to explore the expression of ras, p53 and heat stress protein 70 (HSP70) in 29 patients with PAHs-related lung cancer (LC), and 28 patients with non-cancerous pulmonary disease, and 30 healthy controls.The positive detection rates of P21, P53, and HSP70 in LC group (58.62%, 34.48%, 41.38% respectively) were higher than those in non-cancerous pulmonary disease group (14.29%, 7.14%, 10.71% respectively, P0.01). The sensitivity of P21, P53 and HSP70 were 58.62%, 34.48% and 41.38% respectively, negative predictive value (NPV) were 68.42%, 78.05% and 63.04% respectively. The co-detection of the three proteins mentioned above produced a sensitivity of 82.76% with a NPV of 78.26% (P0.05). Of 18 cases of LC with negative cytology, 13 (72.22%) were found HSP21, P53 or HSP70 positive.Co-detection of the P21, P53, and HSP70 may be used as the screening marker for diagnosis of PAHs-related lung cancer, and may supplement the diagnostic value of conventional cytology.

To explore the effect of benzo(a)pyrene (BaP) on the expression and the activities of cytochrome P450 1A1 (CYP1A1) of porcine aortic endothelial cells.Porcine aortic endothelial cells were cultured in vitro, and treated with different concentrations of BaP (0, 0.5, 1.0, 5.0, 10.0 micro mol/L) for 24 hours, CYP1A1 expression was determined by Western blot and immunohistochemistry. At the same time, the ethoxyresorufin-o-deethylase (EROD) activities were measured by spectrofluorometer.By Western blot, the expression of CYP1A1 of control cells was not found, but the expression of CYP1A1 of cells treated with BaP was found; By immunohistochemistry, only part of endothelial cells treated with BaP had positive expression of CYP1A1. The peak activities of EROD induced by BaP was at the concentration of 0.5 - 1.0 micro mol/L.BaP could induce part of endothelial cells to synthesize CYP1A1. BaP of 0.5 - 1.0 micro mol/L could induce peak activities of EROD.