A Systematic Assessment of Blood Lead Level in Children and Associated Risk Factors in China / 生物医学与环境科学（英文）

In this study, we searched multiple databases for all relevant original articles (1996-2013). To investigate blood lead levels (BLL) and possible risk factors for lead exposure among children in China A total of 388 articles met our inclusion criteria. The overall geometric mean (GM) BLL was 71 µg/L, and the prevalence of elevated BLL (EBLL, defined as BLL ⋝ 100 µg/L) was 18.48% among children. The prevalence of EBLL remained significantly higher among boys. In children less than 6 years of age, there were significantly increasing trends in both BLL and prevalence of EBLL in an age-dependent manner. The ban on leaded gasoline significantly reduced the BLL as well as EBLL prevalence; however, children whose parents had lower educational levels or were exposed to lead in the workplace had a higher EBLL prevalence. Despite its decline over time, the average BLL among children in China remains higher than the average level most recently reported in the United States. Childhood lead poisoning remains a public health problem in China.

Inhibition of DNA-dependent protein kinase catalytic subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis / 华中科技大学学报（医学）（英德文版）

Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.

Inhibition of DNA-dependent protein kinase catalytic subunit by small molecule inhibitor NU7026 sensitizes human leukemic K562 cells to benzene metabolite-induced apoptosis / 华中科技大学学报（医学）（英德文版）

Benzene is an established leukotoxin and leukemogen in humans. We have previously reported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to mediate the cellular response to DNA double strand break (DSB) caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026), as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phosphorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apoptosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.

Effect of TTRAP expression on apoptosis induced by hydroquinone in HL-60 cells in vitro / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effect of TTRAP expression on apoptosis induced by hydroquinone in HL-60 cells in vitro, and explore the relationship between TTRAP expression and the apoptosis.</p><p><b>METHODS</b>Apoptotic and necrotic rate was examined by flow cytometer with Anti-AnnexinV/FITC Plus PI staining. The mRNA expression of TTRAP was detected by RT-PCR. The differences in different treated groups were compared.</p><p><b>RESULTS</b>After different concentrations of hydroquinone to the cells for 0, 4, 8, 12 h culture, were added, the cell apoptotic rate in different concentrations of hydroquinone groups was significantly higher than that in blank control groups. The optimal concentration of hydroquinone was 200 micromol/L, lasting for 8 h. When it was 250 micromol/L, the necrotic rate increased significantly. The apoptosis induced by hydroquinone was associated with the culture time at the concentration of 200 micromol/L, and the peak apoptotic time was 8 h. Then the apoptotic rate decreased and necrotic rate increased. Furthermore, with the concentrations of hydroquinone increased and time lasted for 8 h, the apoptotic rate of cells increased, the amount of TTRAP expression in the mRNA level also increased accordingly. When the concentrations of hydroquinone was above 250 micromol/L, necrotic rate increased sharply, and the amount of TTRAP expression decreased.</p><p><b>CONCLUSION</b>Hydroquinone could induce apoptosis of HL-60 cells. The up-regulation of TTRAP expression may promote hydroquinone to induce HL-60 cells to go into apoptosis in vitro with dose-effect and time-effect relationship.</p>

Significant positive correlation of plasma BPDE-albumin adducts to urinary 1-hydroxypyrene in coke oven workers / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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; P<0.01). 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, P<0.01) and urinary 1-OHP levels above 4.13 micromol/mol creatinine (OR=2.45, P<0.05). There was a positive correlation between the levels of BPDE-albumin adducts and urinary 1-OHP in all subjects (rs=0.349, P<0.01).</p><p><b>CONCLUSION</b>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.</p>

Protective effect of tert-butylhydroquinone on bone marrow cells in rats from cytotoxicity induced by benzene in vitro / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of tert-butylhydroquinone on bone marrow cells in rats from cytotoxicity induced by benzene in vitro.</p><p><b>METHODS</b>The bone marrow cells in rats were divided into two groups randomizedly. Cells of the control group were stimulated by 0, 5, 10, 15, 20 mmol/L benzene for 2, 4, 6 hours respectively. Cells of the tBHQ-pretreated group were treated by 100 micromol/L tBHQ for 12 hours followed by the same conditions as the control group. The DNA damage was detected by single cell gel electrophoresis assay (SCGE) and cell apoptosis was examined by flow cytometry. The activities of NAD (P) H: quinone oxidoreductase (NQO1) in bone marrow cells of rats were also measured before benzene treatment in two groups.</p><p><b>RESULTS</b>In control group, the DNA damage and the apoptosis of bone marrow cells was increased with the growing concentration and time of benzene treatment. The DNA migration and the lengths of DNA migration of the bone marrow cells in the rats under 5, 10, 15, 20 mmol/L benzene treatment in the tBHQ-pretreated group were significantly lower than those in control group at the same time point (P < 0.05). The apoptosis of the bone marrow cells in the rats stimulated by 15, 20 mmol/L benzene for 2 hours and 10, 15, 20 mmol/L benzene for 4 hours as well as 5, 10, 15, 20 mmol/L benzene for 6 hours were also significantly lower than those in control group (P < 0.05). The activities of NQO1 in the bone marrow cells in the rats were increased after tBHQ treatment (P < 0.01) (1.62 +/- 0.16 min(-1).mg(-1) vs. the control group: 0.95 +/- 0.08 min(-1).mg(-1)).</p><p><b>CONCLUSION</b>The benzene can induce the DNA damage and the apoptosis of bone marrow cells in rats in a time dependent and dose dependent manner to some extent. The tBHQ can protect the bone marrow cells in rats from the cytotoxicity induced by benzene, which can be partly explained by the increase of the NQO1 activity induced by tBHQ.</p>

Detection of apoptosis genes differentially expressed in patients with different degrees of benzene poisoning by cDNA microarray / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the differential expression of apoptosis genes in patients with different degrees of benzene poisoning by cDNA microarray.</p><p><b>METHODS</b>Peripheral mononuclear cells were isolated from seven patients with benzene poisoning of different degrees (suspected 1 case, moderate 2, severe 2), and seven age and sex matched normal control subjects. Total RNA was extracted and purified, followed by reverse transcription to cDNAs with concomitant incorporation of fluorescent dCTP (Cy3 or Cy5). Then 177 genes associated with cell apoptosis were hybridized against the cDNAs probes in microarray. Fluorescent signals were scanned to detect apoptosis genes differentially expressed in patients and normal subjects.</p><p><b>RESULTS</b>Forty one genes were found to be differentially expressed between benzene-poisoned patients and normal controls; among the 41 genes, three were up-regulated among patients with mild to moderate degrees of benzene poisoning and one up-regulated among all patients. The total amount of differentially expressed genes of apoptosis decreased with the aggravation of benzene poisoning.</p><p><b>CONCLUSIONS</b>Differential expression of apoptosis genes was found in patients with benzene poisoning, suggesting a role of altered apoptosis in benzene-induced hematotoxicity.</p>

cDNA microarray to identify the significance of DNA replication and damage repair genes associated with benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To screen DNA replication, and damage repair genes associated with benzene poisoning by using gene expression profile analysis.</p><p><b>METHODS</b>Leucocytes in peripheral blood of seven patients and seven normal controls were collected and total RNA was extracted. The cDNA probes were prepared by labeling cell RNA with Cy3-dUTP and Cy5-dUTP with reverse transcription. The arrays with 141 genes were hybridized against the cDNA probe mixture, and the fluorescent signals were scanned.</p><p><b>RESULTS</b>Twenty five differentially expressed genes were screened out. Among these genes, 16 genes were up-regulated and 9 down-regulated. They were DNA replication genes such as PRIM2A, ORC1L etc; DNA synthesis, recombination and repair genes such as POLK etc; DNA damage signaling/repair proteins and DNA ligases such as RECQL, PRKDC, G22P1, ERCC3, ERCC1, CRY1, CHES1, BRCA2, APEX etc; proteins involved in recombination such as RECQL; and other DNA synthesis, recombination, and repair proteins such as SKIV2L, RBMS1, SON, SET.</p><p><b>CONCLUSIONS</b>Some DNA replication, and damage repair genes associated with benzene poisoning show differential expression, which provides the basis for screening biomarkers of benzene poisoning.</p>

Analysis on tumor related gene expression profiles in benzene poisoning using cDNA microarray / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To detect target genes for further study by way of analyzing the gene expression profiles of benzene poisoning by using cDNA microarray.</p><p><b>METHODS</b>Peripheral mononuclear cells were isolated from seven patients with benzene poisoning of different degrees, and sevene age-and sex-matched normal subjects. Total RNA was extracted and purified, followed by revese transcription to cDNAs with concomitant incorporation of fluorescent dCTP (Cy3 or Cy5). The cDNAs were used as probes in microarray of 2780 cloned cDNA. Fluorescent signals were scanned to detect genes differentially expressed in patients and normal subjects.</p><p><b>RESULTS</b>Among 7 pieces of cDNA microarray of 2780 tumour related genes, the expression of 16 genes, such as GRO1, TGFBR3, LYN ctc was upregulated, whereas the expression of 28 genes, such as FOSB, DJ-1, MCT-1 etc was down-regulated.</p><p><b>CONCLUSION</b>Abnormal expression of tumour related genes of patients exposed to benzene suggests that they may be the key genes, which play important role in benzene-induced leucocythemia. cDNA microarray technique is useful to indicate the expression mode of benzene poisoning tumour related genes, and to find rapidly and effectively new research object and the way of gene therapy.</p>