The cytotoxic effect of cadmium is studied by detecting intracellular nicotinamide adenine dinucleotidea(NADH) autofluorescence in this work. NADH autofluorescence in processes of cadmium-induced apoptosis, necrosis...The cytotoxic effect of cadmium is studied by detecting intracellular nicotinamide adenine dinucleotidea(NADH) autofluorescence in this work. NADH autofluorescence in processes of cadmium-induced apoptosis, necrosis and reversible injury are recorded timely. The relativity between time course of NADH autofluorescence and cadmium toxicity is established. The cell toxicity effect of Cadmium on yeast cells is studied by detecting the time courses of intracellular reduced NADH autofluorescence in this work. The relativity between time courses of NADH autofluorescence and Cadmium toxicity is established.展开更多
The selective toxicity of the mitochondria-specific cationic fluorescent dye rhodamine 123 (Rh-123) on He La cells in culture was studied. In this report, we demonstrate that with continuous exposure, Rh-123 markedly ...The selective toxicity of the mitochondria-specific cationic fluorescent dye rhodamine 123 (Rh-123) on He La cells in culture was studied. In this report, we demonstrate that with continuous exposure, Rh-123 markedly inhibited the growth of HeLa cells but had little effect on normal human kidney fibroblasts. With continuous exposure to Rh-123, the growth rate, colony forming ability, anl mitotic index of HeLa cells were decreased. The mechanism of toxicity of Rh-123 on HeLa cells was investigated by EM and enzyme cytochemistry stain. The mitochondria of carcinoma cells were the main targets for the inhibitory action of Rh-123, since they selectively accumulated the dye. At the dosage of Rh-123 which was toxic to HeLa cells, the structure and function of mitochondria were disrupted, as the mitochondria-related enzymes, i.e., ATPase, LDH and SDH were inhibited. The possible mechanism of the action of Rh-123 on HeLa cells is briefly discussed.展开更多
This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of v...This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.展开更多
While CrylAc has been known to bind with larval midgut proteins cad- herin, APN (amino peptidase N), ALP (alkaline phosphatase) and ABCC2 (adenosine triphosphate-binding cassette transporter subfamily C2), littl...While CrylAc has been known to bind with larval midgut proteins cad- herin, APN (amino peptidase N), ALP (alkaline phosphatase) and ABCC2 (adenosine triphosphate-binding cassette transporter subfamily C2), little is known about the recep- tors of Cry2Ab. To provide a clue to the receptors of Cry2Ab, we tested the baseline cytotoxicity of activated Cry 1Ac and Cry2Ab against the midgut and fat body cell lines of Helicoverpa zea and the ovary cell line ofSpodopterafrugiperda (SFg). As expected, the descending order of cytotoxicity of CrylAc against the three cell lines in terms of 50% lethal concetration (LC50) was midgut (31.0μg/mL) 〉 fat body (59.0μg/mL) and SF9 cell (99.6μg/mL). By contrast, the fat body cell line (LC50 = 7.55μg/mL) was about twice more susceptible to Cry2Ab than the midgut cell line (16.0/xg/mL), the susceptibility of which was not significantly greater than that of SF9 cells (27.0μg/mL). Further, ligand blot showed the binding differences between CrylAc and Cry2Ab in the three cell lines. These results indicated that the receptors of Cry2Ab were enriched in fat body cells and thus largely different from the receptors of CrylAc, which were enriched in midgut cells.展开更多
The adverse effects of environmental pollution on our well-being have been intensively studied with many in vitro and in vivo systems. In our group, we focus on stem cell toxicology due to the multitude of embryonic s...The adverse effects of environmental pollution on our well-being have been intensively studied with many in vitro and in vivo systems. In our group, we focus on stem cell toxicology due to the multitude of embryonic stem cell(ESC) properties which can be exerted in toxicity assays. In fact, ESCs can differentiate in culture to mimic embryonic development in vivo, or specifically to virtually any kind of somatic cells. Here, we used the toxicant Bisphenol A(BPA), a chemical known as a hazard to infants and children, and showed that our stem cell toxicology system was able to efficiently recapitulate most of the toxic effects of BPA previously detected by in vitro system or animal tests. More precisely, we demonstrated that BPA affected the proper specification of germ layers during our in vitro mimicking of the embryonic development, as well as the establishment of neural ectoderm and neural progenitor cells.展开更多
The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products(DBPs). Many of the identified DBPs exhibit in...The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products(DBPs). Many of the identified DBPs exhibit in vitro and in vivo toxicity, generate a diversity of adverse biological effects, and may be hazards to the public health and the environment.Only a few DBPs are regulated by several national and international agencies and it is not clear if these regulated DBPs are the forcing agents that drive the observed toxicity and their associated health effects. In this study, we combine analytical chemical and biological data to resolve the forcing agents associated with mammalian cell cytotoxicity of drinking water samples from three cities. These data suggest that the trihalomethanes(THMs) and haloacetic acids may be a small component of the overall cytotoxicity of the organic material isolated from disinfected drinking water. Chemical classes of nitrogen-containing DBPs, such as the haloacetonitriles and haloacetamides, appear to be the major forcing agents of toxicity in these samples. These findings may have important implications for the design of epidemiological studies that primarily rely on the levels of THMs to define DBP exposure among populations. The TIC-Tox approach constitutes a beginning step in the process of identifying the forcing agents of toxicity in disinfected water.展开更多
There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is ...There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is limited information available on their effects on neural development(Betts,2010;US EPA,2015).展开更多
Objective To assess the efficacy of Rh-endostatin plus the combination of gemcitabine/navelbine and cisplatin in patients with non-small cell lung cancer (NSCLC).Methods NSCLC patients,not receiving chemotherapy,were ...Objective To assess the efficacy of Rh-endostatin plus the combination of gemcitabine/navelbine and cisplatin in patients with non-small cell lung cancer (NSCLC).Methods NSCLC patients,not receiving chemotherapy,were divided into two groups.Then they were given the combination of gemcitabine/navelbine and cisplatin with or without Rh-endostatin at 2-week intervals for 4 treatment cycles.Results Forty patients were enrolled and all of them were assessable for response and toxicity.None had complete response but 4 patients had partial response.An overall response rate was 10%.The survival rate was 65% at 1 year,with a median survival time of 16.2 months.Hematological complications were the most common toxic reactions,with grade≥3 reactions occurring at rates of 7%,7%,4% and 2%,respectively.Conclusion Rh-endostatin may have anti-tumor activity with high clinical benefit rate and is well tolerated in lung cancer with stage Ⅲb/Ⅳ.Compared with single combination of gemcitabine/navelbine and cisplatin,no more significant unexpected adverse events were observed.展开更多
Disinfection by-products occur widely as the unintended effect of water disinfection and are associated with toxicity and adverse human health effects. Yet the molecular mechanisms of their toxicity are not well under...Disinfection by-products occur widely as the unintended effect of water disinfection and are associated with toxicity and adverse human health effects. Yet the molecular mechanisms of their toxicity are not well understood. To investigate the molecular basis of hyperploidy induction by monohaloacetonitriles, the interaction of monohaloacetonitriles with topoisomerase Ⅱ in Chinese hamster ovary cells was examined. We showed a concentration-dependent inhibition of DNA decatenation activity of topoisomerase under acellular conditions while in vitro monohaloacetonitrile treatment expressed mixed results. The working hypothesis, that topoisomerase Ⅱ is a molecular target of monohaloacetonitriles, was only partially supported.Nevertheless, this research serves as a starting point toward molecular mechanisms of toxic action of monohaloacetonitriles.展开更多
基金Supported by the National Natural Science Foundation of China (20275027)
文摘The cytotoxic effect of cadmium is studied by detecting intracellular nicotinamide adenine dinucleotidea(NADH) autofluorescence in this work. NADH autofluorescence in processes of cadmium-induced apoptosis, necrosis and reversible injury are recorded timely. The relativity between time course of NADH autofluorescence and cadmium toxicity is established. The cell toxicity effect of Cadmium on yeast cells is studied by detecting the time courses of intracellular reduced NADH autofluorescence in this work. The relativity between time courses of NADH autofluorescence and Cadmium toxicity is established.
文摘The selective toxicity of the mitochondria-specific cationic fluorescent dye rhodamine 123 (Rh-123) on He La cells in culture was studied. In this report, we demonstrate that with continuous exposure, Rh-123 markedly inhibited the growth of HeLa cells but had little effect on normal human kidney fibroblasts. With continuous exposure to Rh-123, the growth rate, colony forming ability, anl mitotic index of HeLa cells were decreased. The mechanism of toxicity of Rh-123 on HeLa cells was investigated by EM and enzyme cytochemistry stain. The mitochondria of carcinoma cells were the main targets for the inhibitory action of Rh-123, since they selectively accumulated the dye. At the dosage of Rh-123 which was toxic to HeLa cells, the structure and function of mitochondria were disrupted, as the mitochondria-related enzymes, i.e., ATPase, LDH and SDH were inhibited. The possible mechanism of the action of Rh-123 on HeLa cells is briefly discussed.
文摘This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.
文摘While CrylAc has been known to bind with larval midgut proteins cad- herin, APN (amino peptidase N), ALP (alkaline phosphatase) and ABCC2 (adenosine triphosphate-binding cassette transporter subfamily C2), little is known about the recep- tors of Cry2Ab. To provide a clue to the receptors of Cry2Ab, we tested the baseline cytotoxicity of activated Cry 1Ac and Cry2Ab against the midgut and fat body cell lines of Helicoverpa zea and the ovary cell line ofSpodopterafrugiperda (SFg). As expected, the descending order of cytotoxicity of CrylAc against the three cell lines in terms of 50% lethal concetration (LC50) was midgut (31.0μg/mL) 〉 fat body (59.0μg/mL) and SF9 cell (99.6μg/mL). By contrast, the fat body cell line (LC50 = 7.55μg/mL) was about twice more susceptible to Cry2Ab than the midgut cell line (16.0/xg/mL), the susceptibility of which was not significantly greater than that of SF9 cells (27.0μg/mL). Further, ligand blot showed the binding differences between CrylAc and Cry2Ab in the three cell lines. These results indicated that the receptors of Cry2Ab were enriched in fat body cells and thus largely different from the receptors of CrylAc, which were enriched in midgut cells.
基金supported by a Chinese Academy of Sciences(CAS)Strategic Leading Science&Technology Program grant(XDB14040301)by the Hundred Talent Program of CAS(121311ZXPP2014004)at the Research Center for Eco-Environmental Sciences(RCEES),CAS
文摘The adverse effects of environmental pollution on our well-being have been intensively studied with many in vitro and in vivo systems. In our group, we focus on stem cell toxicology due to the multitude of embryonic stem cell(ESC) properties which can be exerted in toxicity assays. In fact, ESCs can differentiate in culture to mimic embryonic development in vivo, or specifically to virtually any kind of somatic cells. Here, we used the toxicant Bisphenol A(BPA), a chemical known as a hazard to infants and children, and showed that our stem cell toxicology system was able to efficiently recapitulate most of the toxic effects of BPA previously detected by in vitro system or animal tests. More precisely, we demonstrated that BPA affected the proper specification of germ layers during our in vitro mimicking of the embryonic development, as well as the establishment of neural ectoderm and neural progenitor cells.
文摘The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products(DBPs). Many of the identified DBPs exhibit in vitro and in vivo toxicity, generate a diversity of adverse biological effects, and may be hazards to the public health and the environment.Only a few DBPs are regulated by several national and international agencies and it is not clear if these regulated DBPs are the forcing agents that drive the observed toxicity and their associated health effects. In this study, we combine analytical chemical and biological data to resolve the forcing agents associated with mammalian cell cytotoxicity of drinking water samples from three cities. These data suggest that the trihalomethanes(THMs) and haloacetic acids may be a small component of the overall cytotoxicity of the organic material isolated from disinfected drinking water. Chemical classes of nitrogen-containing DBPs, such as the haloacetonitriles and haloacetamides, appear to be the major forcing agents of toxicity in these samples. These findings may have important implications for the design of epidemiological studies that primarily rely on the levels of THMs to define DBP exposure among populations. The TIC-Tox approach constitutes a beginning step in the process of identifying the forcing agents of toxicity in disinfected water.
基金the Canada Research Chairs Program,the Canadian Institutes of Health Research,and the Natural Sciences and Engineering Research Council of Canada for their support
文摘There is little to no toxicity information regarding thousands of chemicals to which people are exposed daily.In fact,of the84,000 chemicals listed in the United States Toxic Substances Control Act Inventory,there is limited information available on their effects on neural development(Betts,2010;US EPA,2015).
文摘Objective To assess the efficacy of Rh-endostatin plus the combination of gemcitabine/navelbine and cisplatin in patients with non-small cell lung cancer (NSCLC).Methods NSCLC patients,not receiving chemotherapy,were divided into two groups.Then they were given the combination of gemcitabine/navelbine and cisplatin with or without Rh-endostatin at 2-week intervals for 4 treatment cycles.Results Forty patients were enrolled and all of them were assessable for response and toxicity.None had complete response but 4 patients had partial response.An overall response rate was 10%.The survival rate was 65% at 1 year,with a median survival time of 16.2 months.Hematological complications were the most common toxic reactions,with grade≥3 reactions occurring at rates of 7%,7%,4% and 2%,respectively.Conclusion Rh-endostatin may have anti-tumor activity with high clinical benefit rate and is well tolerated in lung cancer with stage Ⅲb/Ⅳ.Compared with single combination of gemcitabine/navelbine and cisplatin,no more significant unexpected adverse events were observed.
基金supported by NSF STC Water CAMPWS (Award CTS-0120978)the U.S.EPA STAR Grant R834867funded in part by the U.S.Environmental Protection Agency's STAR program
文摘Disinfection by-products occur widely as the unintended effect of water disinfection and are associated with toxicity and adverse human health effects. Yet the molecular mechanisms of their toxicity are not well understood. To investigate the molecular basis of hyperploidy induction by monohaloacetonitriles, the interaction of monohaloacetonitriles with topoisomerase Ⅱ in Chinese hamster ovary cells was examined. We showed a concentration-dependent inhibition of DNA decatenation activity of topoisomerase under acellular conditions while in vitro monohaloacetonitrile treatment expressed mixed results. The working hypothesis, that topoisomerase Ⅱ is a molecular target of monohaloacetonitriles, was only partially supported.Nevertheless, this research serves as a starting point toward molecular mechanisms of toxic action of monohaloacetonitriles.