OBJECTIVE To find the infla mmation bio markers induced by coke oven e missions (COE),we investigated the changes of T helper 17 (Th17 )cytokines in hu man bronchial epithelial (16HBE)cells.METHODS 16HBE cells were exposed to organic extracts of COE collected fro m co-king plant at the concentrations of 5,10 and 20 mg·L -1 for 24 h or 5 d to establish short-term and long-term cell models,respectively.Cell viability was measured by MTT assay and infla mmatory da mage was assessed by lactate dehydrogenase assay (LDH).The cytokines in culture supernatant sa mples was detected by co mmercial hu man Th17 cytokine panel kit.RESULTS COE Can induce infla mmation in COE 20 mg·L -1 group and no expression on IL-17 F and IL-1 β.The concentration of IL-10 was 1 .25 ± 0.54,1 .39 ±0.13 and (1 .90 ±0.73)pg·mL -1 in COE 5,10 and 20 mg·L -1 group showing good con-centration-effect relationship (r=0.98,P <0.05 ).IL-23 expression was found only higher at 10 and 20 mg·L -1 and the concentrations were 3.38 ±3.90 and (1 .74 ±2.00 )pg·mL -1 ,respectively.In 16HBE cells treated by COE for 5 d,elevated expression of IL-17A was found in COE 5 and 10 mg·L -1 group,and there was statistically sigificant difference between COE 10 mg·L -1 and DMSO group (P<0.05).Elevated concentration of IL-17F of 10.2 ±1 1 .78 and (6.79 ±7.84)pg·mL -1 was found in COE 5 and 10 mg·L -1 group.The concentration of IL-10 was 1 .71 ±0.02,1 .49 ±0.25 and (2.82 ± 0.33)pg·mL -1 in COE 5,10 and 20 mg·L -1 group,respectively.We found increased IL-1 βexpression with concentration of 2.72 ±0.62,2.25 ±0.33 and (0.93 ±0.21 )pg·mL -1 in COE 5,10 and 20 mg·L -1 group with negative dose-response relationship.We also found more elevated TNF-αlevels in the 5 d than in the 24 h model with no COE specific relationship.CONCLUSION COE induces expression changes of Th17 cytokines profile in 16HBE cells,including IL-23 and IL-1 βfor early and long-term infla mmation,respectively.IL-10 may be a candidate marker for population study on COE induced infla mmatory injury.

OBJECTIVETo estimate the reference value for micronucleus frequency of peripheral blood lymphocytes in general Chinese population, and to guide the genotoxicity evaluation and risk analysis for populations exposed to environmental or occupational chemicals.

METHODSA fulltext search was performed in CNKI with the key words of "micronucleus" and "human", and PubMed was searched with "cytokinesis-block micronucleus","CBMN","humans", and "adults", to obtain the articles published at home and abroad from 2001 to 2014 in which cytokinesis-block micronucleus (CBMN)assay was applied for micronucleus detection and populations not exposed to genotoxins were established as a control. Monte Carlo simulation was performed based on the micronucleus frequency, standard deviation, and sample size provided in these articles to calculate the micronucleus frequency for general population and to analyze the influence of sex, smoking, and drinking on micronucleus frequency.

RESULTSA total of 23 articles were included in the final analysis. The minimum mean micronucleus frequency was 0.39‰, and the maximum mean micronucleus frequency was 25.3‰. There were 1623 subjects in the control group in total (range 22~178, mean 70.6). Monte Carlo simulation was performed 100 times, and the mode of micronucleus frequency was 0 or 1‰; the values of P0, P25, P50 , P75, and P95 were 0‰, 1‰, 2‰~3‰, 5‰~6‰, and 14‰~19‰, respectively; the mean value was 4.36‰(range 4.22‰~4.57‰). With the application of one-sided 95% range(x±1.64 s), the upper limit of the range of reference value was calculated to be 13.46‰~14.75‰.

CONCLUSIONThe micronucleus frequency of peripheral blood lymphocytes in general Chinese population is 4.36‰, the interquartile range is 1‰~5‰ or 1‰~6‰, and the upper limit of reference value is 14.17‰. The factors of living area, sex, smoking, and drinking may influence micronucleus frequency.

Adult ; Alcohol Drinking ; DNA Damage ; Environment ; Humans ; Lymphocytes ; pathology ; Micronucleus Tests ; Monte Carlo Method ; Mutagens ; Reference Values ; Sex Factors ; Smoking

OBJECTIVE: To observe the levels of four hydroxylated metabolites of polycyclic aromatic hydrocarbons(PAHs)in the urine of coke workers and its influencing factors.To explore the feasibility of using PAHs as biomarkers for exposure of coke oven emissions(COEs).METHODS: A cross-sectional survey was used to compare 261 coke oven workers in a coke oven plant as exposure group with 111 workers without COEs exposure in an oxygen making plant as control group.Ultra high liquid chromatography-mass spectrometry was used to detect four hydroxylated metabolites of PAHs,including1-hydroxypyrene(OHP),1-hydroxynaphthalene(OHN),2-OHN and 3-hydroxyphenanthrene,in urine of these two groups.RESULTS: The levels of four hydroxylated metabolites of PAHs in urine in exposure group were higher than that of the control group(P<0.01).The levels of urinary 1-OHP,1-OHN,2-OHN were followed by the sequence of bottomoven,side-oven,and top-oven subgroups among the exposure group(P<0.05).The multiple linear regression results indicated that the levels of urinary 1-OHP,1-OHN,2-OHN were correlated with COEs exposure(P<0.05),after adjusting the confounding factors of gender,age,length of service,smoking status and alcohol drinking status.The levels of urinary 1-OHP,1-OHN,2-OHN of the exposure group increased with the increase of COEs exposure levels showing a dose-effect relationship(P<0.01).The levels of 1-OHN and 2-OHN were associated with smoking apart from COEs exposure(P<0.01).CONCLUSION: The urinary 1-OHP can be used as a reliable biomarker for the evaluation of internal exposure to COEs.The 1-OHN and 2-OHN can be used as adjuvant biomarkers.

OBJECTIVETo systematically evaluate the environmental exposure information of coke oven workers, we investigated the concentration and size distribution characteristics of the particle matter (PM) in the top working area of coke oven.

METHODSThe aerodynamic particle sizer spectrometer was employed to collect the concentration and size distribution information of PM at a top working area. The PM was divided into PM ≤ 1.0 µm, 1.0 µm < PM ≤ 2.5 µm, 2.5 µm < PM ≤ 5.0 µm, 5.0 µm < PM ≤ 10.0 µm and PM>10.0 µm based on their aerodynamic diameters. The number concentration, surface area concentration, and mass concentration were analyzed between different groups. We also conducted the correlation analysis on these parameters among groups.

RESULTSWe found the number and surface area concentration of top area particulate was negatively correlated with particle size, but mass concentration curve showed bimodal type with higher point at PM = 1.0 µm and PM = 5.0 µm. The average number concentration of total particulate matter in the top working area was 661.27 number/cm³, surface area concentration was 523.92 µm²/cm³, and mass concentration was 0.12 mg/m³. The most number of particulate matter is not more than 1 µm (PM(1.0)), and its number concentration and surface area concentration accounted for 96.85% and 67.01% of the total particles respectively. In the correlation analysis, different particle size correlated with the total particulate matter differently. And the characteristic parameters of PM2.5 cannot fully reflect the total information of particles.

CONCLUSIONThe main particulate matter pollutants in the top working area of coke oven is PM1.0, and it with PM(5.0) can account for a large proportion in the mass concentration of PM. It suggest that PM1.0 and PM(5.0) should be considered for occupational health surveillance on the particulate matter in the top area of coke oven.

Air Pollutants, Occupational ; analysis ; Coke ; Humans ; Occupational Exposure ; analysis ; Particle Size ; Particulate Matter ; analysis ; Workplace

Objective: To investigate the association between etheno-DNA adduct and the promoter of DNA methylation levels of cyclin dependent kinase inhibitor 2A (P16), Ras association domain family 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in workers with occupational exposure to diesel engine exhaust (DEE). Methods: We recruited 124 diesel engine testing workers as DEE exposure group and 112 water pump operator in the same area as control group in Henan province in 2012 using cluster sampling. The demographic data were obtained by questionnaire survey; urine after work and venous blood samples were collected from each subject. The urinary etheno-DNA adducts were detected using UPLC-MS/MS, including 1,N6-etheno-2'-deoxyadenosine (εdA) and 3,N4-etheno-2'-deoxycytidine(εdC). The DNA methylation levels of P16, RASSF1A, and MGMT were evaluated using bisulfite-pyrosequencing assay. The percentage of methylation was expressed as the 5-methylcytosine (5mC) over the sum of cytosines (%5mC). Spearman correlation and multiple linear regression were applied to analyze the association between etheno-DNA adducts and DNA methylation of P16, RASSF1A, and MGMT. Results: The median (P₂₅-P₇₅) of urinary εdA level was 230.00 (98.04-470.91) pmol/g creatinine in DEE exposure group, and 102.10 (49.95-194.48) creatinine in control group. The level of εdA was higher in DEE exposure group than control group (P<0.001). DNA methylation levels of P16, RASSF1A and MGMT were 2.04±0.41, 2.19 (1.94-2.51), 2.22 (1.94-2.46)%5mC in exposure group, and 2.19±0.40, 2.41 (2.11-2.67), 2.44 (2.15-2.91)%5mC in control group. DNA methylation levels were lower in exposure group (P values were 0.005, 0.002 and 0.001, respectively). Spearman correlation analysis showed that DNA methylation levels of P16, RASSF1A, and MGMT were negative associated with urinary εdA level (r values were -0.155, -0.137, and -0.198, respectively, P<0.05). No significant correlation was observed between the εdC level and any measured DNA methylation levels (P>0.05) . Multiple linear regression confirmed the negative correlation between εdA and DNA methylation levels of P16, RASSF1A, and MGMT in non-smoking group (β (95%CI) was -0.068 (-0.132--0.003), -0.082 (-0.159--0.004) and -0.048 (-0.090--0.007), P values were 0.039, 0.039 and 0.024, respectively). Moreover, εdC was negative associated with DNA methylation level of MGMT in non-smoking group (β (95%CI) was -0.094 (-0.179--0.008), P=0.032). Conclusion DEE exposure could induce the increased of εdA and decreased of DNA methylation levels of P16, RASSF1A and MGMT.

OBJECTIVETo investigate the cell proliferation and genome stability in workers with occupational exposure to diesel exhaust (DE).

METHODSIn 2012, 117 DE-exposed workers and 106 control workers were recruited by cluster sampling in this study. The demographic data were obtained by questionnaire survey. The airborne fine particle and enriched polycyclic aromatic hydrocarbons (PAHs) at different workplaces were collected and analyzed. The concentrations of main PAHs monohydroxy metabolites in the urine were determined by high performance liquid chromatography-mass spectrometry (LC-MS), which could reflect the internal exposure level of DE. The cell proliferation capacity and genome stability in the periphery lymphocytes of workers were evaluated by cytokinesis-block micronucleus (CBMN) cytome assay.

RESULTSThe concentrations (median (P5-P95)) of total PAHs monohydroxy metabolites in the urine of exposed group and control group were 12.96 (4.73-28.10), 4.76 (0.90-15.00) µg/L, respectively, and the exposed group was higher than that of controls (Z = -8.77, P < 0.001). The nuclear division index (NDI) of exposed group and control group was 1.68±0.13, 1.85±0.16, respectively, and the NDI of exposed group showed significantly decreased (t = 8.86, P < 0.001), while the genome instability index calculated by micronucleus, nuclear bridges and nuclear buds, of exposed group and control group was 13.27±6.26, 4.83±3.38, respectively, and the exposed group had statistically significant increase (Z = -10.08, P < 0.001). The tertiles of total PAHs monohydroxy metabolites in the urine were categorized into low, medium and high groups (<5.96, 5.96-12.46, >12.46 µg/L). With the NDI decreased, 1.81±0.17, 1.79±0.17, 1.68±0.14 (F = 13.14, P < 0.001), genome instability index began to increase 5.80±4.15, 9.97±7.14, 11.99±6.61 (/1 000), respectively (χ(2) = 36.74, P < 0.001). With the increase of total PAHs monohydroxy metabolites level in corresponding groups. In addition, the NDI was negatively correlated with the frequencies of micronucleus, nuclear bridges, nuclear buds and genome instability index, respectively, and the difference was statistically significant (P < 0.001).

CONCLUSIONSDE exposure lead to inhibition of cell proliferation capacity and increase genome instability in the peripheral lymphocytes of occupational-exposed population, providing important clues and evidence for early biomarkers monitoring.

Biomarkers ; Cell Proliferation ; Chromatography, Liquid ; Genomic Instability ; Humans ; Lymphocytes ; Micronucleus Tests ; Occupational Exposure ; Particulate Matter ; Polycyclic Aromatic Hydrocarbons ; Surveys and Questionnaires ; Vehicle Emissions ; Workplace

OBJECTIVETo investigate the role of myelin protein zero (P(0)) in 2,5-hexanedione (2,5-HD)-induced peripheral nerve injury, and the protective effect of Ginkgo biloba extract (Egb761) on 2,5-HD-induced toxic peripheral neuropathy.

METHODSAfter 4 weeks of treatment with 2,5-HD at different doses (50, 100, 200, 400 mg/kg) in rats, changes in the levels of P(0) in rat sciatic nerves was investigated, and the effect of Egb761 on 2,5-HD-induced toxic peripheral neuropathy was studied.

RESULTSThe blood-nerve barrier (BNB) permeability of the sciatic nerve increased, and the expression of P(0) mRNA and P(0) protein decreased in a dose-dependent manner after treatment with 2,5-HD for 4 weeks. Pretreatment with Egb761 protected against BNB interruption, and inhibited P(0) mRNA and protein reduction during 2,5-HD treatment. Pretreatment with Egb761 significantly reduced loss of body weight (P<0.01) and mitigated gait abnormalities (2.85±0.22) induced by 400 mg/kg 2,5-HD (P<0.01). It also reduced the signs of neurotoxicity induced by 2,5-HD.

CONCLUSION2,5-HD inhibited the expression of P(0) in a dose-dependent manner, and this may be an important mechanism by which toxic peripheral neuropathy is induced by 2,5-HD. Egb761 has a protective effect against 2,5-HD-induced peripheral neurotoxicity in rats.

Animals ; Dose-Response Relationship, Drug ; Environmental Pollutants ; toxicity ; Gene Expression Regulation ; drug effects ; Hexanones ; toxicity ; Male ; Myelin P0 Protein ; genetics ; metabolism ; Neuroprotective Agents ; pharmacology ; Plant Extracts ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Sciatic Nerve ; drug effects

Objective Mitochondrial DNA depletion syndrome is a rare autosomal recessive disorder characterized by complex genetic and clinical manifestations.This study aimed to investigate the clinical and laboratory features of a boy with mitochondrial encephalomyopathy caused by SUCLG1 mutation.Methods The clinical data and genetic test of a patient with mitochondrial DNA depletion syndrome were retrospectively analyzed.Result The proband presented with limb weakness at the 4th month after birth,and presented dystrophic appearance,muscular hypotonia,psychomotor retardation,failure to thrive,hearing impairment,scoliosis,thoracocyllosis and facial features at 9 months old.Laboratory tests showed blood lactic acid and pymvate increased,liver damage and abnormal myocardial enzymes.Plasma camitine ester profiling showed that amino acids decreased and C4-dicarboxylic-carnitine increased.Urinary organic acid analysis showed increased concentration of methylmalonic acid and its metabolites indicating methyl malonic aciduria.MRI showed bilateral T2 hyperintensities in bilateral caudate nuelei and lenticular and brain atrophy-like changes.Brainstem auditory evoked potential showed severe hearing loss.His development quotient was 35.Genetic sequencing of MUT,,MMAA,MMAB and other classic mitochondrial disease related genes of the proband revealed no mutation.Two heterozygous mutations,c.961C＞G and c.713T＞C,inherited from the phenotype of normal parents were detected in his SUCLG1 gene.The copy number of mitochondrial DNA was 244/cell in peripheral blood leukocytes,equivalent to 68.4％ of that in normal control.Conclusion In this study,an infant with muscular hypotonia,psychomotor retardation,deafness and slightly increased urine methyl malonic acid was diagnosed by genetic test.For patients with unexplained hypotonia,mental retardation,abnormal movements,hearing disorder together with increased blood pyruvic acid and lactic acid,mild methylmalonic acidemia and abnormal acylcarnitine,mitochondrial DNA depletion syndrome should be considered.Gene analysis is important for diagnosis and prenatal diagnosis of the next pregnancy.

Adverse outcome pathway (AOP) was a conceptual construct that integrated existing knowledge concerning the pathway of causal linkages between a molecular initiating event (MIE) and a final adverse effect at individual or population levels. The AOP methodology could be used as a basis for effects extrapolation and was an approach towards providing a framework for collecting and evaluating relevant chemical, biological and toxicological information. The framework would play an important role in risk assessment. We reviewed the concept of AOP, the development and assessment of the framework and the established models in toxicology researches. And the prospects and challenges of its application in toxicology were also introduced.
Research Design ; Risk Assessment ; Toxicology ; methods

OBJECTIVE: To compare and analyze the risk of formaldehyde hazards in a plywood manufacturing factory using two risk assessment methods,and to evaluate the occupational health risk. METHODS: Occupational health investigation and formaldehyde detection for workplaces were carried out in a plywood manufacturing factory in Shandong province. The risk ratings of different posts were assessed by US Environmental Protection Agency( EPA) inhalation risk( EPA assessment model) and Singapore Semi-quantitative Assessment Model( MOM assessment model). The risk classification results of the 2 risk assessment methods were compared and analyzed. RESULTS: The concentration of airborne formaldehyde on the positions of shaving,woods feeding,gluing,hot milling,hot pressing,sanding and reprocessing were 0. 25,0. 13,1. 47,0. 72,0. 92 and 0. 58 mg/m~3,respectively. By the EPA assessment model,all of the positions were evaluated as high carcinogenic risk. Through the MOM assessment model,the feeding position was evaluated as medium risk,the positions of shaving,hot milling,hot pressing sanding and reprocessing were high risk,and the position of gluing was higher risk. CONCLUSION: It suggests that there is a high formaldehyde exposure in several posts in the plywood production processing. EPA assessment model is a suitable for occupational health risk assessment for formaldehyde exposure.