Guangdong Poison Control Center

Guangzhou, China

Guangdong Poison Control Center

Guangzhou, China
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Tang X.,Guangdong Medical Laboratory Animal Center | Zhu J.,State University of New York at Buffalo | Zhong Z.,Guangdong Medical Laboratory Animal Center | Luo M.,Guangdong Medical Laboratory Animal Center | And 10 more authors.
Toxicology and Applied Pharmacology | Year: 2016

Chronic exposure to cadmium compounds (Cd2+) is one of the major public health problems facing humans in the 21st century. Cd2+ in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd2+ from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000 mg/kg or 5000 mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd2+ deposited in the kidneys of Cd2+-laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd2+ level was reduced from 12.9 μg/g to 1.3 μg/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd2+ from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd2+ exposure. © 2016 Elsevier Inc.


Tang X.,Guangdong Poison Control Center | Yang X.,Guangdong Poison Control Center | Lai G.,Guangdong Poison Control Center | Guo J.,Sun Yat Sen University | And 14 more authors.
Toxicology | Year: 2010

Trimethyltin chloride (TMT), a byproduct of plastic stabilizers, has caused 67 poisoning accidents in the world; more than 98% (1814/1849) of the affected patients since 1998 have been in China. As a long-established toxic chemical, TMT severely affects the limbic system and the cerebellum; however, its relationship with hypokalemia, a condition observed in the majority of the cases in the last decade, remains elusive. To understand the mechanism underlying hypokalemia induced by TMT, Sprague-Dawley (SD) rats were administered TMT to determine the relationship between H+/K+-ATPase activity and the blood and urine K+ concentration and pH, respectively. H+/K+-ATPase protein and mRNA were observed too. In vitro changes to intracellular pH, K+ channels in renal cells were measured. The results showed that TMT increased potassium leakage from the kidney, raised urine pH, and inhibited H+/K+-ATPase activity both in vitro and in vivo. In the tested animals, H+/K+-ATPase activity was positively correlated with the decrease of plasma K+ and blood pH but was negatively correlated with the increase of urine K+ and urine pH (P<0.01), while TMT did not change the expression of H+/K+-ATPase protein and mRNA. TMT decreased intracellular pH and opened K+ channels in renal intercalated cells. Our findings suggest TMT can directly inhibit the activity of H+/K+-ATPases in renal intercalated cells, reducing urine K+ reabsorption and inducing hypokalemia. © 2010 Elsevier Ireland Ltd.


Shuga J.,University of California at Berkeley | Zeng Y.,University of California at Berkeley | Zeng Y.,University of Kansas | Novak R.,University of California at San Francisco | And 10 more authors.
Nucleic Acids Research | Year: 2013

Cancers are heterogeneous and genetically unstable. New methods are needed that provide the sensitivity and specificity to query single cells at the genetic loci that drive cancer progression, thereby enabling researchers to study the progression of individual tumors. Here, we report the development and application of a bead-based hemi-nested microfluidic droplet digital PCR (dPCR) technology to achieve 'quantitative' measurement and single-molecule sequencing of somatically acquired carcinogenic translocations at extremely low levels (<10-6) in healthy subjects. We use this technique in our healthy study population to determine the overall concentration of the t(14;18) translocation, which is strongly associated with follicular lymphoma. The nested dPCR approach improves the detection limit to 1 × 10-7 or lower while maintaining the analysis efficiency and specificity. Further, the bead-based dPCR enabled us to isolate and quantify the relative amounts of the various clonal forms of t(14;18) translocation in these subjects, and the single-molecule sensitivity and resolution of dPCR led to the discovery of new clonal forms of t(14;18) that were otherwise masked by the conventional quantitative PCR measurements. In this manner, we created a quantitative map for this carcinogenic mutation in this healthy population and identified the positions on chromosomes 14 and 18 where the vast majority of these t(14;18) events occur. © 2013 The Author(s).


Hosgood H.D.,U.S. National Cancer Institute | Zhang L.,University of California at Berkeley | Tang X.,Guangdong Poison Control Center | Vermeulen R.,University Utrecht | And 23 more authors.
American Journal of Industrial Medicine | Year: 2013

Background: Formaldehyde is used in many occupational settings, most notably in manufacturing, health care, and embalming. Formaldehyde has been classified as a human carcinogen, but its mechanism of action remains uncertain. Methods: We carried out a cross-sectional study of 43 formaldehyde-exposed workers and 51 unexposed age and sex-matched controls in Guangdong, China to study formaldehyde's early biologic effects. To follow up our previous report that the total lymphocyte count was decreased in formaldehyde-exposed workers compared with controls, we evaluated each major lymphocyte subset (i.e., CD4+ T cells, CD8+ T cells, natural killer [NK] cells, and B cells) and T cell lymphocyte subset (CD4+ naïve and memory T cells, CD8+ naïve and memory T cells, and regulatory T cells). Linear regression of each subset was used to test for differences between exposed workers and controls, adjusting for potential confounders. Results: Total NK cell and T cell counts were about 24% (P=0.037) and 16% (P=0.0042) lower, respectively, among exposed workers. Among certain T cell subsets, decreased counts among exposed workers were observed for CD8+ T cells (P=0.026), CD8+ effector memory T cells (P=0.018), and regulatory T cells (CD4+FoxP3+: P=0.04; CD25+FoxP3+: P=0.008). Conclusions: Formaldehyde-exposed workers experienced decreased counts of NK cells, regulatory T cells, and CD8+ effector memory T cells; however, due to the small sample size; these findings need to be confirmed in larger studies. © 2012 Wiley Periodicals, Inc.


Tang X.,Guangdong Medical Laboratory Animal Center | Tang X.,Guangdong Poison Control Center | Li N.,Centers for Disease Control and Prevention | Kang L.,Guangdong Medical Laboratory Animal Center | And 15 more authors.
Occupational and Environmental Medicine | Year: 2013

Objectives: Nephrolithiasis (kidney stones) is a common disease with the prevalence that is increasing globally. We previously found that trimethyltin (TMT), a by-product of plastic stabilisers, can inhibit the H+/K + ATPase activity in renal intercalated cells and alter urinary pH, which is a known risk factor for nephrolithiasis. In this study, we conducted a crosssectional analysis to evaluate the impact of chronic low level occupational TMT exposure on nephrolithiasis. Methods: This study included 216 healthy workers with TMT exposure and 119 workers as controls with no TMT exposure. All study participants were administered a questionnaire and underwent a routine clinical examination including an ultrasonographic screening for kidney stones. Exposures were assessed by measuring TMT concentrations in personal air samples, blood and urine. Logistic regression analysis was used to estimate the ORs and 95% CIs for the risk of kidney stones. Results: TMT exposed workers had a higher prevalence of kidney stones (18.06%) in comparison with control workers (5.88%). High TMT concentrations in personal air samples, blood and urines were positively associated with increased prevalence of kidney stones in workers exposed to TMT compared with controls workers (p-trend values=0.005, 0.008 and 0.002, respectively). The length of employment in plants with elevated TMT levels (duration of the exposure) was significantly associated with the increased prevalence of kidney stones (p trend=0.001). The ORs were 2.66 for <3 years, 3.73 for 3-<10 years and 7.89 for 10+ years of employment compared with control workers. Conclusions: To our knowledge, this is the first report to demonstrate that occupational exposure to TMT is a potential risk factor for nephrolithiasis.


Vermeulen R.,University Utrecht | Zhang L.,University of California at Berkeley | Spierenburg A.,University Utrecht | Tang X.,Guangdong Poison Control Center | And 21 more authors.
Carcinogenesis | Year: 2012

Epidemiological studies suggest that trichloroethylene (TCE) exposure may be associated with renal cancer. The biological mechanisms involved are not exactly known although nephrotoxicity is believed to play a role. Studies on TCE nephrotoxicity among humans, however, have been largely inconsistent. We studied kidney toxicity in Chinese factory workers exposed to TCE using novel sensitive nephrotoxicity markers. Eighty healthy workers exposed to TCE and 45 comparable unexposed controls were included in the present analyses. Personal TCE exposure measurements were taken over a 2-week period before urine collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration permissible exposure limit (100 ppm 8h TWA), with a mean (SD) of 22.2 (35.9) ppm. Kidney injury molecule-1 (KIM-1) and Pi-glutathione S transferase (GST) alpha were elevated among the exposed subjects as compared with the unexposed controls with a strong exposure-response association between individual estimates of TCE exposure and KIM-1 (P < 0.0001). This is the first report to use a set of sensitive nephrotoxicity markers to study the possible effects of TCE on the kidneys. The findings suggest that at relatively low occupational exposure levels a toxic effect on the kidneys can be observed. This finding supports the biological plausibility of linking TCE exposure and renal cancer. Abbreviations: GSTglutathione-S-transferase. KIM-1kidney injury molecule-1. NAGN-acetyl-beta-(d)-glucosaminidaseOVMorganic vapour monitoring. TCEtrichloroethylene. VEGFvascular endothelial growth factor. © The Author 2012. Published by Oxford University Press. All rights reserved.


Lan Q.,U.S. National Cancer Institute | Zhang L.,University of California at Berkeley | Tang X.,Guangdong Poison Control Center | Shen M.,U.S. National Cancer Institute | And 21 more authors.
Carcinogenesis | Year: 2010

Occupational cohort and case-control studies suggest that trichloroethylene (TCE) exposure may be associated with non-Hodgkin lymphoma(NHL) but findings are not consistent. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. We carried out a cross-sectional molecular epidemiology study of 80 healthy workers that used TCE and 96 comparable unexposed controls in Guangdong, China. Personal exposure measurements were taken over a three-week period before blood collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration Permissible Exposure Limit (100 p.p.m. 8 h time-weighted average), with a mean (SD) of 22.2 (36.0) p.p.m. The total lymphocyte count and each of the major lymphocyte subsets including CD4+ T cells, CD8+ T cells, natural killer (NK) cells and B cells were significantly decreased among the TCE-exposed workers compared with controls (P < 0.05), with evidence of a dosedependent decline. Further, there was a striking 61% decline in sCD27 plasma level and a 34% decline in sCD30 plasma level among TCE-exposed workers compared with controls. This is the first report that TCE exposure under the current Occupational Safety and Health Administration workplace standard is associated with a decline in all major lymphocyte subsets and sCD27 and sCD30, which play an important role in regulating cellular activity in subsets of T, B and NK cells and are associated with lymphocyte activation. Given that altered immunity is an established risk factor for NHL, these results add to the biologic plausibility that TCE is a possible lymphomagen. Published by Oxford University Press 2010.


Zhang L.,University of California at Berkeley | Bassig B.A.,U.S. National Cancer Institute | Mora J.L.,University of California at Berkeley | Vermeulen R.,University Utrecht | And 19 more authors.
Carcinogenesis | Year: 2013

Trichloroethylene (TCE) has been associated with a variety of immunotoxic effects and may be associated with an increased risk of non-Hodgkin lymphoma (NHL). Altered serum immunoglobulin (Ig) levels have been reported in NHL patients and in animals exposed to TCE. Recently, we reported that occupational exposure to TCE is associated with immunosuppressive effects and immune dysfunction, including suppression of B-cell counts and activation, even at relatively low levels. We hypothesized that TCE exposure would also affect Ig levels in humans. We measured serum levels of IgG, IgM and IgE, by enzyme-linked immunosorbent assay, in TCE-exposed workers (n = 80) and unexposed controls (n = 45), matched by age and gender, in a cross-sectional, molecular epidemiology study of occupational exposure to TCE in Guangdong, China. Exposed workers had about a 17.5% decline in serum levels of IgG compared with unexposed controls (P = 0.0002). Similarly, serum levels of IgM were reduced by about 38% in workers exposed to TCE compared with unexposed controls (P < 0.0001). Serum levels of both IgG and IgM were significantly decreased in workers exposed to TCE levels below 12 p.p.m., the median exposure level. Adjustment for B-cell counts had minimal impact on our findings. IgE levels were not significantly different between exposed and control subjects. These results provide further evidence that TCE is immunotoxic at relatively low exposure levels and provide additional biologic plausibility for the reported association of TCE with NHL. © The Author 2012. Published by Oxford University Press. All rights reserved.


PubMed | Guangdong Medical Laboratory Animal Center, Sun Yat Sen University, Golden Health Foshan Technology Co., State University of New York at Buffalo and Guangdong Poison Control Center
Type: | Journal: Toxicology and applied pharmacology | Year: 2016

Chronic exposure to cadmium compounds (Cd(2+)) is one of the major public health problems facing humans in the 21st century. Cd(2+) in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd(2+) from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000mg/kg or 5000mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd(2+) deposited in the kidneys of Cd(2+)-laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd(2+) level was reduced from 12.9g/g to 1.3g/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd(2+) from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd(2+) exposure.

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