Screening serum biomarkers for occupational exposure to titanium dioxide nanoparticles using metabolomics / 中国职业医学

OBJECTIVE: To screen the serum biomarkers in workers occupationally exposed to titanium dioxide nanoparticles(TiO_2 NPs) using metabolomics technology. METHODS: Using a typical sampling method, 56 workers who have occupationally exposed to TiO_(2 )in a TiO_2 NPs manufacturer were selected as the exposure group and 44 employees without occupational exposure to TiO_2 were selected as the control group. The high performance liquid chromatography-mass spectrometry technology was used to perform non-targeted metabolomics detection. The difference in serum metabolite profiles of the TiO_2 NPs exposure group and the control group were analyzed. Key differential metabolites and potential biomarkers were screened. The sensitivity and specificity of biomarkers were assessed through receiver operating characteristic(ROC) curve.RESULTS: We detected a total of 1 492 mass spectrum peaks in serum samples by serum metabolomics analysis, and 413 well-matched metabolites were obtained after annotation and identification. The results of principal component analysis and orthogonal partial least squares discriminant analysis showed that a total of 296 differentially expressed metabolites were found in the serum of individuals of the exposure group compared with the control group(all P<0.01). Among them the relative expression of metabolites increased in 265 species and decreased in 31 species. The ROC analysis results showed that the area under the ROC curve of five metabolites exceeded 0.900, and these metabolites included tanacetol A,(5 E)-2-hydroxy-4-oxobenzopenta-5-en-1-ylacetic acid, triterpene saponins organic compounds, 9,10,13-trihydroxystearic acid, and liquoric acid. The multiple linear regression analysis showed that the relative expression of all the five metabolites were positively correlated with occupational exposure to TiO_2 NPs after adjusting for the influence of confounding factors such as gender, age, body mass index, smoking and drinking(all P<0.01). CONCLUSION: Occupational exposure to TiO_2 NPs could induce changes in serum metabolite profiles. The metabolites represented by tanacetol A in serum can be used as potential biomarkers for indicating occupational exposure to TiO_2 NPs.

Biomonitoring application in the exposome assessment / 中华预防医学杂志

Biomonitoring can be applied to assess internal exposure and environmental exposure by exposure markers with providing internal exposure to biological characterization and individual exposure information, which is a key tool to evaluate the risk exposure to disease by biological alternation information. With the development of high throughput, broad spectrum and high efficiency screening and detection technology, biomonitoring is defined as traditional biological monitoring (targeted monitoring) and non targeted monitoring analysis (exposomic approaches). An exposomic approach differs from traditional biomonitoring in that it can theoretically include all exposures of potential health significance, whether they are derived from exogenous sources. Both traditional and nontraditional biomonitoring methods should be used to understand the complexity of exposures faced throughout the lifespan. Through hybrid approaches, emerging techniques and the integration of bioinformatics, and developing the detection methods for low abundance chemicals, improving the differentiation ability between endogenous and exogenous chemical, the health outcomes and exposures can be widely recognized and characterized, which can finally contribute to improving the precise prevention and intervention for diseases under the new exposomic model.

Effects on human peripheral erythrocytes of long-term occupational contact with chromate / 中华预防医学杂志

Objective@#To investigate the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate.@*Methods@#A dynamic cohort study was conducted of chromate-exposed workers (343 cases) and non-chromate-exposed workers (73 cases) at a chromate production enterprise who were selected according to specific inclusion and exclusion criteria from 2010 to 2015. Personal information and chromate exposure information were obtained by questionnaire. A generalized estimating equation was employed to analyze the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate, controlling for age, gender, smoking, alcohol consumption and body mass index.@*Results@#The mean ages and working ages of those entering the cohort study were 36.67 ±6.78 and 38.47 ± 7.18, respectively, for the exposure group and 8.39 ± 6.02 and 12.86 ± 8.34, respectively, for the control group. The erythrocyte content [(4.73±0.46), (4.81±0.53), (4.41±0.45)]×1012/L in the peripheral blood in the chromate exposure group was lower than that [(4.76±0.42), (4.95±0.45), (4.47±0.39)]×1012/L in the control group for the years 2010, 2011, 2012 and 2014 (t values were 0.38, 1.96, 0.92 and 1.21; P values were 0.703, 0.051, 0.358 and 0.227, respectively). The correlations between the years 2010 and 2011, 2011 and 2012, 2012 and 2014, and 2014 and 2015 were 0.667, 0.464,-0.070 and 0.020, respectively (P<0.001). The RR for males and those that consumed alcohol were 0.661 (95% CI: 0.616-0.709) and 0.910 (95% CI: 0.811- 1.201), respectively. Compared with the control group, the risk of reduced erythrocyte levels in the peripheral blood was increased by 0.915 (95% CI: 0.852- 0.982) in the chromate-exposed group.@*Conclusions@#The erythrocyte content of peripheral blood was reduced after long-term exposure to chromate. Maleness and alcohol consumption were factors that increased the risk of reduced peripheral blood erythrocytes in the chromate-exposed population.

Effect of nano-TiO2 on intestinal glucose absorption in young rat on the everted gut sac model / 北京大学学报(医学版)

Objective: To study the effect of titanium dioxide (TiO2) nanoparticles on intestinal glucose absorption in young rats and its size effect.Methods: In the study, 63 small intestine segments were isolated from 63 Sprague-Dawley rats (SD rats, 4-week-old) to prepare the everted gut sac model.In the first part of our work, the everted sacs were exposed to 0, 50 mg/L TiO2 nanoparticles (24 nm) for 2 h with the presence of a series of glucose concentrations (10, 25, 50, 100, 200, 400, and 800 mmol/L), and the glucose absorbing function of the everted sacs were assessed in the process.On the basis of the work, utilizing the same method, further study was carried out to compare the effects of TiO2 nanoparticles (24 nm) and fine-particles (120 nm) on intestinal glucose absorbing function with the presence of 400 mmol/L glucose and 0, 10, 50, 200 mg/L TiO2.3 intestine segments were used in each group.Results: The cumulative glucose absorption increased with time extension and increased glucose concentration.In the first part of our work, with the presence of 400 mmol/L glucose, the group treated with 50 mg/L TiO2 nanoparticles showed significantly lower cumulative glucose absorption and glucose absorbing rate than the control group at the exposure time of 30 min (tcumulative absorption=3.254, P<0.05;tglucose absorbing rate=3.958, P<0.05), 90 min (tcumulative absorption=3.323, P<0.05;tglucose absorbing rate=3.063, P<0.05) and 120 min (tcumulative absorption=2.834, P<0.05;tglucose absorbing rate=3.002, P<0.05).At other glucose concentrations, statistically significant differences in cumulative glucose absorption or glucose absorbing rates were not found between the TiO2 nanoparticle exposed group and the control group.In the second part of our work, when compared with the control group, no significant downregulations in cumulative glucose absorption or glucose absorbing rates were observed in both TiO2 nano-particle treated group and TiO2 fine particle treated group.Differences between the TiO2 nanoparticle treated group and the TiO2 fine particle treated group were not statistically significant.Conclusion: Short-term exposure to TiO2 nanoparticles may downregulate the intestinal glucose absorbing function in young rats, and the difference with TiO2 fine particlesis is not obvious.

Genotoxic effects of oral-exposed TiO2 nanoparticles on bone marrow cells in young rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the genotoxic effects of oral-exposed TiO2 nanoparticles on bone marrow cells in young rats.</p><p><b>METHODS</b>Twenty-eight SD male young rats (4 weeks old) were randomly divided into 4 groups, which were exposed to TiO2 nanoparticles ((75 ± 15) nm, anatase) through intragastric administration at 0, 10, 50 and 200 mg/kg body weight (bw) every day for 30 days. The bone marrow cells were collected for micronuclei and γ-H2AX immunofluorescence analysis.</p><p><b>RESULTS</b>The percentage of γ-H2AX foci-positive cells (37.4 ± 10.0)% in the 50 mg/kg bw dose group were significantly higher than that in the control group (19.8 ± 3.1)% (t value was -17.59, P < 0.01). No significantly difference was found in polychromatic erythrocyte/normochromatic erythrocyte (PCE/NCE) ratio and PCE micronucleus rate between three experimental groups and control group.</p><p><b>CONCLUSION</b>TiO2 nanoparticles can increase the frequency of DNA double-strand breaks in bone marrow cells, but has no effect on micronucleus of bone marrow cells in young rats.</p>

Effects of TiO2 nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats / 北京大学学报(医学版)

Objective:To compare the effect of TiO 2 nanoparticles on antioxidant function and element content of liver and kidney tissues in young and adult rats .Methods:Forty-eight SD male rats , half in 4-week (youth) old and half in 9-week (adult) old rats, were randomly divided into 8 groups, which were exposed to TiO2 nanoparticles [(75 ±15) nm, anatase] through intragastric administration at 0, 10, 50 and 200 mg/kg body weight every day for 30 days.The liver and kidney tissues were collected for antioxidant function and element content analysis .Results: 200 mg/kg TiO2 nanoparticles exposure significantly increased the liver total superoxide dismutase ( T-SOD ) activity and the kidney reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios in young rats, and significantly decreased the liver Mo, Co, Mn and P contents and the kidney Rb and Na contents in young rats .200 mg/kg TiO2 nanoparticles exposure significantly increased GSH/GSSG ratios and Rb contents and decreased Na con-tents in the liver of adult rats .No significantly difference was found in antioxidant indexes and elements content in the kidney of adult rats between three experimental groups and control group .Conclusion:TiO2 nanoparticles can enhance the antioxidant capacity and decrease the elements content in rat liver and kidney tissues .The liver is the more sensitive target organ and the young animals are more susceptible to TiO2 nanoparticles toxicity by the oral routes .