RNA Sequencing Analyses Reveal the Potential Mechanism of Pulmonary Injury Induced by Gallium Arsenide Particles in Human Bronchial Epithelioid Cells.

Extensive use of gallium arsenide (GaAs) has led to increased exposure to humans working in the semiconductor industry. This study employed physicochemical characterization of GaAs obtained from a workplace, cytotoxicity analysis of damage induced by GaAs in 16HBE cells, RNA-seq and related bioinformatic analysis, qRT-PCR verification and survival analysis to comprehensively understand the potential mechanism leading to lung toxicity induced by GaAs. We found that GaAs-induced abnormal gene expression was mainly related to the cellular response to chemical stimuli, the regulation of signalling, cell differentiation and the cell cycle, which are involved in transcriptional misregulation in cancer, the MAPK signalling pathway, the TGF-ß signalling pathway and pulmonary disease-related pathways. Ten upregulated genes (FOS, JUN, HSP90AA1, CDKN1A, ESR1, MYC, RAC1, CTNNB1, MAPK8 and FOXO1) and 7 downregulated genes (TP53, AKT1, NFKB1, SMAD3, CDK1, E2F1 and PLK1) related to GaAs-induced pulmonary toxicity were identified. High expression of HSP90AA1, RAC1 and CDKN1A was significantly associated with a lower rate of overall survival in lung cancers. The results of this study indicate that GaAs-associated toxicities affected the misregulation of oncogenes and tumour suppressing genes, activation of the TGF-ß/MAPK pathway, and regulation of cell differentiation and the cell cycle. These results help to elucidate the molecular mechanism underlying GaAs-induced pulmonary injury.

Independent effect of main components in particulate matter on DNA methylation and DNA methyltransferase: A molecular epidemiology study.

BACKGROUND: There is a paucity of mechanistic information on the DNA methylation and particulate matter (PM) exposure. This study aimed to investigate the association of PM and its component with DNA methylation, and the roles of DNA methyltransferase (DNMTs). METHODS: There were 240 high-exposed, 318 low-exposed and 210 non-exposed participants in this study. Individual concentrations of PM, polycyclic aromatic hydrocarbons (PAHs) and metals were identified by the monitoring data in their workplaces. Urinary 1-OHP and metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1, DNMT3A and DNMT3B were measured. We used mediation analysis to evaluate the role of DNMTs expression on DNA methylation alteration induced by PAHs and metals components. RESULTS: The decreasing trend of % 5mC was associated with increment of PM exposure in all subjects. We found that one IQR increase in total PAHs (3.82 µg/m3) and urinary 1-OHP (1.06 µmol/mol creatinine) were associated with a separate 6.08% and 7.26% decrease in % 5mC (P = 0.009, P < 0.001), and one IQR increase in urinary Ni (27.75 µmol/mol creatinine) was associated with a 3.29% decrease in % 5mC (P = 0.03). The interaction of urinary 1-OHP with Ni on global DNA methylation (%5mC) was not found (P interaction = 0.89). PM exposure was significantly associated with decreased mRNA level of DNMT3B, but the mediated effect of the PAHs and Ni levels on % 5mC through the DNMT3B pathway was not observed. CONCLUSIONS: We found the decrement of global DNA methylation and DNMT3B expression with elevated PM levels in population. The independent mode of action on DNA hypomethylation was found from PAHs and metal components. Global DNA hypomethylation might be a potential biomarker for evaluation of adverse health effects in response to PM exposure.

Analysis of Blood Concentrations of Zinc, Germanium, and Lead and Relevant Environmental Factors in a Population Sample from Shandong Province, China.

Trace elements, including zinc (Zn) and germanium (Ge), are essential for health; deficiency or excess levels of trace elements results is harmful. As a result of industrial and agricultural production, Pb widely exists in people's living environment. It is absorbed mainly through the respiratory and digestive tracts, producing systemic harm. Reference values for a normal, healthy population are necessary for health assessment, prevention and treatment of related diseases, and evaluation of occupational exposures. Reference ranges for the Chinese population have not been established. From March 2009 to February 2010; we collected data and blood samples (n = 1302) from residents aged 6-60 years living in Shandong Province, China. We measured blood concentrations of Zn, Ge, and Pb using inductively coupled plasma mass spectrometry to determine reference ranges. Results were stratified by factors likely to affect the concentrations of these trace elements: sex, use of cosmetics or hair dye, age, alcohol intake, smoking habits, and consumption of fried food. The overall geometric mean (GM) concentrations (95% confidence interval) were 3.14 (3.08-3.20) mg/L for Zn, 19.9 (19.3-20.6) µg/L for Ge, and 24.1 (23.2-25.1) µg/L for Pb. Blood Zn concentrations were higher in women than in men (p < 0.001), while the opposite was found for Pb (p < 0.001) and sex did not influence Ge (p = 0.095). Alcohol use was associated with higher blood concentrations of Zn (p = 0.002), Ge (p = 0.002), and Pb (p = 0.001). The GM concentration of Zn was highest in 20-30-year-olds (p < 0.001), while Pb concentrations were highest in 12-16-year-olds (p < 0.001). Use of hair dye was associated with lower blood concentrations of Ge (p < 0.05). GM blood concentrations of Pb differed significantly between those who consumed fried foods 1-2 times/month (18.7 µg/L), 1-2 times/week (20.9 µg/L), and every day (28.5 µg/L; p < 0.001). Blood Pb concentrations were higher in subjects who used cosmetics (p < 0.05), hair dye (p < 0.05), and who smoked cigarettes (p < 0.001) than in those who did not.

[Gas chromatography for determination of N-isopropylaniline in workplace atmosphere].

OBJECTIVE: To establish a method for determination of N-isopropylaniline in the workplace atmosphere by gas chromatography. METHODS: Air samples were collected by silica gel tube and desorbed by acetone. Then they were separated through DB-WAX columns and N-isopropylaniline was determined by flame ionization detector. RESULTS: The concentration of N-isopropylaniline showed a good linear relationship within the range of 1.40∼665.0 µg/ml. The sampling efficiency was 100%. The accuracy was 96%∼ 99% and the precision was 2.1%∼7.0%. The minimum detectable concentration was 0.056 mg/m(3) (with sampled air volume of 7.5 L). CONCLUSION: The method meets the requirements of analysis and applies to the determination of N-isopropylaniline in the workplace atmosphere.

Baseline blood levels of manganese, lead, cadmium, copper, and zinc in residents of Beijing suburb.

Baseline blood concentrations of metals are important references for monitoring metal exposure in environmental and occupational settings. The purpose of this study was to determine the blood levels of manganese (Mn), copper (Cu), zinc (Zn), lead (Pb), and cadmium (Cd) among the residents (aged 12-60 years old) living in the suburb southwest of Beijing in China and to compare the outcomes with reported values in various developed countries. Blood samples were collected from 648 subjects from March 2009 to February 2010. Metal concentrations in the whole blood were determined by ICP-MS. The geometric means of blood levels of Mn, Cu, Zn, Pb and Cd were 11.4, 802.4, 4665, 42.6, and 0.68 µg/L, respectively. Male subjects had higher blood Pb than the females, while the females had higher blood Mn and Cu than the males. There was no gender difference for blood Cd and Zn. Smokers had higher blood Cu, Zn, and Cd than nonsmokers. There were significant age-related differences in blood levels of all metals studied; subjects in the 17-30 age group had higher blood levels of Mn, Pb, Cu, and Zn, while those in the 46-60 age group had higher Cd than the other age groups. A remarkably lower blood level of Cu and Zn in this population as compared with residents of other developed countries was noticed. Based on the current study, the normal reference ranges for the blood Mn were estimated to be 5.80-25.2 µg/L; for blood Cu, 541-1475 µg/L; for blood Zn, 2349-9492 µg/L; for blood Pb, <100 µg/L; and for blood Cd, <5.30 µg/L in the general population living in Beijing suburbs.

[Distribution of copper and zinc level in urine of general population in eight provinces of China].

OBJECTIVE: To describe the distribution of zinc (Zn) and copper (Cu) in urine samples of generalpopulation in eight provinces of China, to analyze their characteristics of distribution between different region, gender and age-cohorts, and to provide the baseline of themetabolites in the general population. METHODS: From 2009 to 2010, 18 120 subjects from the general population aged from 6 to 60 years old were recruited from 24 areas among 8 provinces of China mainland by random sampling. The environmental and physical condition characteristics were collected from questionnaires, and urine samples were collected at the mean time. The levels of Zn and Cu in urine were measured using ICP-MS. Data were analyzed by statistical methods to compare the distribution characteristics of Zn and Cu among populations with different ages and genders. RESULTS: Totally, the median of Cu and Zn in urine were 9.28 and 115.47 µg/L respectively; and the inter-quartile range of Cu and Zn were 2.66-16.09 and 35.32-265.15 µg/L respectively. The median of Cu in male and female were 9.90 and 8.60 µg/L (Z=-5.63, P<0.001), and Zn in male and female were 140.44 and 95.27 µg/L (Z=-14.79, P<0.001). The median of Cu among the groups aged 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were 9.30, 10.14, 9.67, 9.33, 8.38 and 8.74 µg/L (χ2=70.94, P<0.001), respectively, and the median of Zn 130.83, 132.07, 139.34, 109.3, 78.74 and 109.51 µg/L ((χ2=146.00, P<0.001), respectively.There was statistically significant differences in urinary Cu and Zn levels between male and female, and among the different age groups. CONCLUSION: The Cu and Zn levels and distribution in urine among general population between 2009 and 2010 in China were reported in this article. These basic data in China will provide scientific and reliable reference for further scientific research.

[Distribution of copper and zinc in blood among general population from 8 provinces in China].

OBJECTIVE: To investigate the level of zinc (Zn) and copper (Cu) in whole blood among general population from 8 provinces in China, and to analyze the characteristics of distribution among different regions. METHODS: This cross-sectional study was performed in 8 provinces from eastern, middle and western China between 2009 and 2010, including 13 110 subjects from 24 regions, and the blood and urine samples were collected. The ICP-MS was applied to test the content of ICP-MS in blood samples, and the results were used to analyze the characteristics of contents and distributions of Zn and Cu among population from different ages, genders and regions groups. RESULTS: Totally, the mean (95%CI) contents of Cu and Zn in blood were 795 (791-799)µg/L and 3 996(3 976-4 015) µg/L, respectively. The characteristics of distribution of Cu content were as followed, the content of males were lower than it of females (male:767 µg/L; female: 822 µg/L, t = -13.302, P < 0.01). The contents of blood Cu in groups of people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 860(853-868), 758(748-769), 734(728-734), 782(774-790), 811(795-827) and 820(815-826) µg/L. The differences showed statistical significance (F = 78.77, P < 0.01). The blood Cu content of people in eastern China (800µg/L) were also significantly higher than it in middle (774 µg/L)and western China (782 µg/L) (F = 10.94, P < 0.01). Distribution of blood Zn content showed characteristics as follows: the Zn content was higher in males than in females (male 4 085 µg/L and female 3 908 µg/L, t = 8.78, P < 0.01). The contents of blood Zn in groups of people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 3 306 (3 261-3 350), 3 888 (3 839-3 937), 3 948 (3 902-3 994), 4 272(4 228-4 315), 4 231(4 180-4 281) and 4 250 (4 205-4 294)µg/L, which showed significant statistical differences (F = 233.68, P < 0.01). The blood Zn content of people in eastern China (3 938 µg/L) were significantly lower than it in middle (4 237 µg/L)and western China (4 105 µg/L) (F = 53.16, P < 0.01). In addition, the study also compared the relation between content of Cu and Zn and the frequency of eating seafood. The results found that the frequency of eating seafood could influence the content of Cu and Zn (Cu: F = 13.54, P < 0.01; Zn: F = 200.20, P < 0.01). CONCLUSION: The contents and distributions of Cu and Zn in blood differs among people from different groups in ages, genders and regions. The baseline data of this study provided reliable scientific evidence for further research.

[Determination of 15 kinds of pesticides in blood by gas chromatography-mass spectrometry].

OBJECTIVE: To develop the method of gas chromatography-mass spectrometry (GC-MS) for simultaneous determination of 15 herbicides in blood. METHODS: 2ml of blood in vitro were sampled, concentrated and extracted with dichloromethane, reconstant with methanol agents of Gulonic acid lactone solution, and detected by GC-MS. RESULTS: Experimental results show that diazinon, atrazine, prometryn, methyl parathion, butachlor, bifenthrin at 4-80 microg/L, phorate, malathion, 2,4-D butyl ester, chlordane, fenpropathrin at 10-200 microg/L, alpha-endosulfan, beta-endosulfan, cyhalothrin at 20-400 microg/L, dimethoate at 40-800 microg/L, with good linear response. The correlation coefficient (r2) were between 0.998-1.000, respectively. The recovery of all analysts averaged between 56%-128% in blood samples. The detection limits of all compounds between 0.05 and 1.00 microg/L. The lower limit of quantification between 0.20 and 3.001 microg/L. CONCLUSION: The methods is apply to detect the content of analysts in blood samples.

[Research the role of gulonic acid lactone in the five kinds of organic phosphorus pesticide detection].

OBJECTIVE: To evaluate the protective effect of gulonic acid lactone in the gas chromatography-mass spectrometry system for detecting phorate, diazinon, dimethoate, methyl parathion, malathion five kinds of organic phosphorus pesticide. METHODS: By comparing the peak area changes of organic phosphorus pesticide configured with different concentrations (0, 0.3, 0.6, 0.9 and 1.2 mg/ml) of the gulonic acid lactone-methanol solution, and the concentrations (500 ng/ml) of organic phosphorus pesticide are same, to determine the best dosage of gulonic acid lactone. In the concentration, evaluate the protective effect of gulonic acid lactone on five kinds of organic phosphorus pesticide testing. RESULTS: When the concentration of gulonic acid lactone-methanol solution <1 mg/ml, the selected ion peak area of the five kinds organophosphorus pesticides detected by gas chromatography-mass spectrometry in the same conditions increases with the upward trend of its concentration ; when the concentration is equal to 1 mg/ml, the peak area reached the highest level, and then with the concentrations increased, no significant change in it. Diazinon's sensitivity increased by 4 times, phorate's sensitivity increased by 5 times, dimethoate, methyl parathion and malathion's sensitivity increased by 10 times, and the peak shape improved distinctly, tailing phenomenon disappears. CONCLUSION: Gulonic acid lactone can effectively improve the five kinds of organic phosphorus pesticide's sensitivity, improving the peak-type tailing and asymmetric phenomenon by the result of the active site. Quantitative bias can be effectively corrected caused by matrix effects. When the concentration is 1 mg/ml, it has the best effect of the compensation effect.