Bromoacetic Acid

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Elizabeth D. Wagner - One of the best experts on this subject based on the ideXlab platform.

  • Haloacetic Acid Water Disinfection Byproducts Affect Pyruvate Dehydrogenase Activity and Disrupt Cellular Metabolism
    Environmental Science & Technology, 2018
    Co-Authors: Azra Dad, Clara H. Jeong, Elizabeth D. Wagner
    Abstract:

    The disinfection of drinking water has been a major public health achievement. However, haloacetic Acids (HAAs), generated as by-products of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown. In this study, we evaluated the effects of mono-, di-, and tri-HAAs on cellular GAPDH enzyme kinetics, cellular ATP levels, and pyruvate dehydrogenase complex (PDC) activity. Here, treatments conducted in Chinese hamster ovary (CHO) cells revealed differences among mono-, di-, and triHAA in their molecular targets. The monoHAAs, iodoacedic Acid and Bromoacetic Acid, were the strongest inhibitors of GAPDH and greatly...

  • Haloacetic Acid Water Disinfection Byproducts Affect Pyruvate Dehydrogenase Activity and Disrupt Cellular Metabolism
    2017
    Co-Authors: Azra Dad, Clara H. Jeong, Elizabeth D. Wagner, Michael J. Plewa
    Abstract:

    The disinfection of drinking water has been a major public health achievement. However, haloacetic Acids (HAAs), generated as byproducts of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown. In this study, we evaluated the effects of mono-, di-, and tri-HAAs on cellular GAPDH enzyme kinetics, cellular ATP levels, and pyruvate dehydrogenase complex (PDC) activity. Here, treatments conducted in Chinese hamster ovary (CHO) cells revealed differences among mono-, di-, and triHAAs in their molecular targets. The monoHAAs, iodoacetic Acid and Bromoacetic Acid, were the strongest inhibitors of GAPDH and greatly reduced cellular ATP levels. Chloroacetic Acid, diHAAs, and triHAAs were weaker inhibitors of GAPDH and some increased the levels of cellular ATP. HAAs also affected PDC activity, with most HAAs activating PDC. The primary finding of this work is that mono- versus multi-HAAs address different molecular targets, and the results are generally consistent with a model in which monoHAAs activate the PDC through GAPDH inhibition-mediated disruption in cellular metabolites, including altering ATP-to-ADP and NADH-to-NAD ratios. The monoHAA-mediated reduction in cellular metabolites results in accelerated PDC activity by way of metabolite-ratio-dependent PDC regulation. DiHAAs and triHAAs are weaker inhibitors of GAPDH, but many also increase cellular ATP levels, and we suggest that they increase PDC activity by inhibiting pyruvate dehydrogenase kinase

  • Monohaloacetic Acid drinking water disinfection by-products inhibit follicle growth and steroidogenesis in mouse ovarian antral follicles in vitro.
    Reproductive Toxicology, 2016
    Co-Authors: Clara H. Jeong, Tyler Dettro, Liying Gao, Elizabeth D. Wagner, William A. Ricke, Jodi Anne Flaws
    Abstract:

    Abstract Water disinfection greatly reduced the incidence of waterborne diseases, but the reaction between disinfectants and natural organic matter in water leads to the formation of drinking water disinfection by-products (DBPs). DBPs have been shown to be toxic, but their effects on the ovary are not well defined. This study tested the hypothesis that monohalogenated DBPs (chloroacetic Acid, CAA; Bromoacetic Acid, BAA; iodoacetic Acid, IAA) inhibit antral follicle growth and steroidogenesis in mouse ovarian follicles. Antral follicles were isolated and cultured with either vehicle or DBPs (0.25–1.00 mM of CAA; 2–15 μM of BAA or IAA) for 48 and 96 h. Follicle growth was measured every 24 h and the media were analyzed for estradiol levels at 96 h. Exposure to DBPs significantly inhibited antral follicle growth and reduced estradiol levels compared to controls. These data demonstrate that DBP exposure caused ovarian toxicity in vitro .

  • energy of the lowest unoccupied molecular orbital thiol reactivity and toxicity of three monobrominated water disinfection byproducts
    Environmental Science & Technology, 2016
    Co-Authors: Justin A. Pals, Elizabeth D. Wagner, Michael Jacob Plewa
    Abstract:

    Disinfection of drinking water protects public health against waterborne pathogens. However, during disinfection, toxic disinfection byproducts (DBPs) are formed. Exposure to DBPs was associated with increased risk of bladder cancer in humans. DBPs are generated at concentrations below their carcinogenic potencies; it is unclear how exposure leads to adverse health outcomes. We used computational estimates of the energy of the lowest unoccupied molecular orbital (ELUMO) to predict thiol reactivity and additive toxicity among soft electrophile DBPs. Bromoacetic Acid (BAA) was identified as non-thiol-reactive, which was supported by in chemico and in vitro data. Bromoacetonitrile (BAN) and bromoacetamide (BAM) were thiol-reactive. Genotoxicity induced by these compounds was reduced by increasing the thiol pool with N-acetyl l-cysteine (NAC), while NAC had little effect on BAA. BAN and BAM shared depletion of glutathione (GSH) or cellular thiols as a molecular initiating event (MIE), whereas BAA induces toxi...

  • Energy of the Lowest Unoccupied Molecular Orbital, Thiol Reactivity, and Toxicity of Three Monobrominated Water Disinfection Byproducts
    2016
    Co-Authors: Justin A. Pals, Elizabeth D. Wagner, Michael J. Plewa
    Abstract:

    Disinfection of drinking water protects public health against waterborne pathogens. However, during disinfection, toxic disinfection byproducts (DBPs) are formed. Exposure to DBPs was associated with increased risk of bladder cancer in humans. DBPs are generated at concentrations below their carcinogenic potencies; it is unclear how exposure leads to adverse health outcomes. We used computational estimates of the energy of the lowest unoccupied molecular orbital (ELUMO) to predict thiol reactivity and additive toxicity among soft electrophile DBPs. Bromoacetic Acid (BAA) was identified as non-thiol-reactive, which was supported by in chemico and in vitro data. Bromoacetonitrile (BAN) and bromoacetamide (BAM) were thiol-reactive. Genotoxicity induced by these compounds was reduced by increasing the thiol pool with N-acetyl l-cysteine (NAC), while NAC had little effect on BAA. BAN and BAM shared depletion of glutathione (GSH) or cellular thiols as a molecular initiating event (MIE), whereas BAA induces toxicity through another pathway. Binary mixtures of BAM and BAN expressed a potentiating effect in genotoxicity. We found that soft electrophile DBPs could be an important predictor of common mechanism groups that demonstrated additive toxicity. In silico estimates of ELUMO could be used to identify the most relevant DBPs that are the forcing factors of the toxicity of finished drinking waters

Michael Jacob Plewa - One of the best experts on this subject based on the ideXlab platform.

  • Water Disinfection Byproducts Increase Natural Transformation Rates of Environmental DNA in Acinetobacter baylyi ADP1.
    Environmental science & technology, 2019
    Co-Authors: David Mantilla-calderon, Stelios Fodelianakis, Grégoire Michoud, Daniele Daffonchio, Michael Jacob Plewa, Pei-ying Hong
    Abstract:

    The process of natural transformation allows for the stable uptake, integration, and functional expression of extracellular DNA. This mechanism of horizontal gene transfer has been widely linked to the acquisition of antibiotic resistance and virulence factors. Here, we demonstrate that Bromoacetic Acid (BAA)-a regulated drinking water disinfection byproduct (DBP)-can stimulate natural transformation rates in the model organism Acinetobacter baylyi ADP1. We demonstrate that transformation stimulation in response to BAA is concentration-dependent and is linked to the ability of this compound to generate DNA damage via oxidative stress. In presence of BAA, transcription of recA was upregulated 20-40% compared to the nontreated controls, indicating that this component of the DNA damage response could be associated with the increase in transformation. Other genes associated with DNA translocation across the cytoplasmic membrane (i.e., pilX, comA) did not exhibit increased transcription in the presence of BAA, indicating that the enhancement of transformation is not associated with increased translocation rates of environmental DNA. Overall, these results lead us to speculate that elevated recA transcription levels could lead to increased integration rates of foreign DNA within the recipient cell during DNA repair. Lastly, we show that an artificial DBP cocktail simulating the environmental concentrations of five water DBP classes stimulates natural transformation by almost 2-fold. The results of this study suggest that mutagens like DBPs may play an important role in enhancing the fixation rates of extracellular DNA in the environmental metagenome.

  • Water Disinfection Byproducts Increase Natural Transformation Rates of Environmental DNA in Acinetobacter baylyi ADP1
    2019
    Co-Authors: David Mantilla-caldero, Stelios Fodelianakis, Grégoire Michoud, Daniele Daffonchio, Michael Jacob Plewa, Pei-ying Hong
    Abstract:

    The process of natural transformation allows for the stable uptake, integration, and functional expression of extracellular DNA. This mechanism of horizontal gene transfer has been widely linked to the acquisition of antibiotic resistance and virulence factors. Here, we demonstrate that Bromoacetic Acid (BAA)a regulated drinking water disinfection byproduct (DBP)can stimulate natural transformation rates in the model organism Acinetobacter baylyi ADP1. We demonstrate that transformation stimulation in response to BAA is concentration-dependent and is linked to the ability of this compound to generate DNA damage via oxidative stress. In presence of BAA, transcription of recA was upregulated 20–40% compared to the nontreated controls, indicating that this component of the DNA damage response could be associated with the increase in transformation. Other genes associated with DNA translocation across the cytoplasmic membrane (i.e., pilX, comA) did not exhibit increased transcription in the presence of BAA, indicating that the enhancement of transformation is not associated with increased translocation rates of environmental DNA. Overall, these results lead us to speculate that elevated recA transcription levels could lead to increased integration rates of foreign DNA within the recipient cell during DNA repair. Lastly, we show that an artificial DBP cocktail simulating the environmental concentrations of five water DBP classes stimulates natural transformation by almost 2-fold. The results of this study suggest that mutagens like DBPs may play an important role in enhancing the fixation rates of extracellular DNA in the environmental metagenome

  • energy of the lowest unoccupied molecular orbital thiol reactivity and toxicity of three monobrominated water disinfection byproducts
    Environmental Science & Technology, 2016
    Co-Authors: Justin A. Pals, Elizabeth D. Wagner, Michael Jacob Plewa
    Abstract:

    Disinfection of drinking water protects public health against waterborne pathogens. However, during disinfection, toxic disinfection byproducts (DBPs) are formed. Exposure to DBPs was associated with increased risk of bladder cancer in humans. DBPs are generated at concentrations below their carcinogenic potencies; it is unclear how exposure leads to adverse health outcomes. We used computational estimates of the energy of the lowest unoccupied molecular orbital (ELUMO) to predict thiol reactivity and additive toxicity among soft electrophile DBPs. Bromoacetic Acid (BAA) was identified as non-thiol-reactive, which was supported by in chemico and in vitro data. Bromoacetonitrile (BAN) and bromoacetamide (BAM) were thiol-reactive. Genotoxicity induced by these compounds was reduced by increasing the thiol pool with N-acetyl l-cysteine (NAC), while NAC had little effect on BAA. BAN and BAM shared depletion of glutathione (GSH) or cellular thiols as a molecular initiating event (MIE), whereas BAA induces toxi...

  • mammalian cell cytotoxicity and genotoxicity of the haloacetic Acids a major class of drinking water disinfection by products
    Environmental and Molecular Mutagenesis, 2010
    Co-Authors: Michael Jacob Plewa, Susan D. Richardson, Jane Ellen Simmons, Elizabeth D. Wagner
    Abstract:

    The haloacetic Acids (HAAs) are disinfection by-products (DBPs) that are formed during the disinfection of drinking water, wastewaters and recreational pool waters. Currently, five HAAs [Bromoacetic Acid (BAA), diBromoacetic Acid (DBAA), chloroacetic Acid (CAA), dichloroacetic Acid (DCAA), and trichloroacetic Acid (TCAA); designated as HAA5] are regulated by the U.S. EPA, at a maximum contaminant level of 60 μg/L for the sum of BAA, DBAA, CAA, DCAA, and TCAA. We present a comparative systematic analysis of chronic cytotoxicity and acute genomic DNA damaging capacity of 12 individual HAAs in mammalian cells. In addition to the HAA5, we analyzed iodoacetic Acid (IAA), diiodoacetic Acid (DiAA), bromoiodoacetic Acid (BIAA), triBromoacetic Acid (TBAA), chlorodiBromoacetic Acid (CDBAA), bromodichloroacetic Acid (BDCAA), and bromochloroacetic Acid (BCAA). Their rank order of chronic cytotoxicity in Chinese hamster ovary cells was IAA > BAA > TBAA > CDBAA > DIAA > DBAA > BDCAA > BCAA > CAA > BIAA > TCAA > DCAA. The rank order for genotoxicity was IAA > BAA > CAA > DBAA > DIAA > TBAA > BCAA > BIAA > CDBAA. DCAA, TCAA, and BDCAA were not genotoxic. The trend for both cytotoxicity and genotoxicity is iodinated HAAs > brominated HAAs > chlorinated HAAs. The use of alternative disinfectants other than chlorine generates new DBPs and alters their distribution. Systematic, comparative, in vitro toxicological data provides the water supply community with information to consider when employing alternatives to chlorine disinfection. In addition, these data aid in prioritizing DBPs and their related compounds for future in vivo toxicological studies and risk assessment. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc.

  • mammalian cell cytotoxicity and genotoxicity of the haloacetic Acids a major class of drinking water disinfection by products
    Environmental and Molecular Mutagenesis, 2010
    Co-Authors: Michael Jacob Plewa, Susan D. Richardson, Jane Ellen Simmons, Elizabeth D. Wagner
    Abstract:

    The haloacetic Acids (HAAs) are disinfection by-products (DBPs) that are formed during the disinfection of drinking water, wastewaters and recreational pool waters. Currently, five HAAs [Bromoacetic Acid (BAA), diBromoacetic Acid (DBAA), chloroacetic Acid (CAA), dichloroacetic Acid (DCAA), and trichloroacetic Acid (TCAA); designated as HAA5] are regulated by the U.S. EPA, at a maximum contaminant level of 60 μg/L for the sum of BAA, DBAA, CAA, DCAA, and TCAA. We present a comparative systematic analysis of chronic cytotoxicity and acute genomic DNA damaging capacity of 12 individual HAAs in mammalian cells. In addition to the HAA5, we analyzed iodoacetic Acid (IAA), diiodoacetic Acid (DiAA), bromoiodoacetic Acid (BIAA), triBromoacetic Acid (TBAA), chlorodiBromoacetic Acid (CDBAA), bromodichloroacetic Acid (BDCAA), and bromochloroacetic Acid (BCAA). Their rank order of chronic cytotoxicity in Chinese hamster ovary cells was IAA > BAA > TBAA > CDBAA > DIAA > DBAA > BDCAA > BCAA > CAA > BIAA > TCAA > DCAA. The rank order for genotoxicity was IAA > BAA > CAA > DBAA > DIAA > TBAA > BCAA > BIAA > CDBAA. DCAA, TCAA, and BDCAA were not genotoxic. The trend for both cytotoxicity and genotoxicity is iodinated HAAs > brominated HAAs > chlorinated HAAs. The use of alternative disinfectants other than chlorine generates new DBPs and alters their distribution. Systematic, comparative, in vitro toxicological data provides the water supply community with information to consider when employing alternatives to chlorine disinfection. In addition, these data aid in prioritizing DBPs and their related compounds for future in vivo toxicological studies and risk assessment.

Clara H. Jeong - One of the best experts on this subject based on the ideXlab platform.

  • Haloacetic Acid Water Disinfection Byproducts Affect Pyruvate Dehydrogenase Activity and Disrupt Cellular Metabolism
    Environmental Science & Technology, 2018
    Co-Authors: Azra Dad, Clara H. Jeong, Elizabeth D. Wagner
    Abstract:

    The disinfection of drinking water has been a major public health achievement. However, haloacetic Acids (HAAs), generated as by-products of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown. In this study, we evaluated the effects of mono-, di-, and tri-HAAs on cellular GAPDH enzyme kinetics, cellular ATP levels, and pyruvate dehydrogenase complex (PDC) activity. Here, treatments conducted in Chinese hamster ovary (CHO) cells revealed differences among mono-, di-, and triHAA in their molecular targets. The monoHAAs, iodoacedic Acid and Bromoacetic Acid, were the strongest inhibitors of GAPDH and greatly...

  • Haloacetic Acid Water Disinfection Byproducts Affect Pyruvate Dehydrogenase Activity and Disrupt Cellular Metabolism
    2017
    Co-Authors: Azra Dad, Clara H. Jeong, Elizabeth D. Wagner, Michael J. Plewa
    Abstract:

    The disinfection of drinking water has been a major public health achievement. However, haloacetic Acids (HAAs), generated as byproducts of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown. In this study, we evaluated the effects of mono-, di-, and tri-HAAs on cellular GAPDH enzyme kinetics, cellular ATP levels, and pyruvate dehydrogenase complex (PDC) activity. Here, treatments conducted in Chinese hamster ovary (CHO) cells revealed differences among mono-, di-, and triHAAs in their molecular targets. The monoHAAs, iodoacetic Acid and Bromoacetic Acid, were the strongest inhibitors of GAPDH and greatly reduced cellular ATP levels. Chloroacetic Acid, diHAAs, and triHAAs were weaker inhibitors of GAPDH and some increased the levels of cellular ATP. HAAs also affected PDC activity, with most HAAs activating PDC. The primary finding of this work is that mono- versus multi-HAAs address different molecular targets, and the results are generally consistent with a model in which monoHAAs activate the PDC through GAPDH inhibition-mediated disruption in cellular metabolites, including altering ATP-to-ADP and NADH-to-NAD ratios. The monoHAA-mediated reduction in cellular metabolites results in accelerated PDC activity by way of metabolite-ratio-dependent PDC regulation. DiHAAs and triHAAs are weaker inhibitors of GAPDH, but many also increase cellular ATP levels, and we suggest that they increase PDC activity by inhibiting pyruvate dehydrogenase kinase

  • Monohaloacetic Acid drinking water disinfection by-products inhibit follicle growth and steroidogenesis in mouse ovarian antral follicles in vitro.
    Reproductive Toxicology, 2016
    Co-Authors: Clara H. Jeong, Tyler Dettro, Liying Gao, Elizabeth D. Wagner, William A. Ricke, Jodi Anne Flaws
    Abstract:

    Abstract Water disinfection greatly reduced the incidence of waterborne diseases, but the reaction between disinfectants and natural organic matter in water leads to the formation of drinking water disinfection by-products (DBPs). DBPs have been shown to be toxic, but their effects on the ovary are not well defined. This study tested the hypothesis that monohalogenated DBPs (chloroacetic Acid, CAA; Bromoacetic Acid, BAA; iodoacetic Acid, IAA) inhibit antral follicle growth and steroidogenesis in mouse ovarian follicles. Antral follicles were isolated and cultured with either vehicle or DBPs (0.25–1.00 mM of CAA; 2–15 μM of BAA or IAA) for 48 and 96 h. Follicle growth was measured every 24 h and the media were analyzed for estradiol levels at 96 h. Exposure to DBPs significantly inhibited antral follicle growth and reduced estradiol levels compared to controls. These data demonstrate that DBP exposure caused ovarian toxicity in vitro .

Michael J. Plewa - One of the best experts on this subject based on the ideXlab platform.

  • Haloacetic Acid Water Disinfection Byproducts Affect Pyruvate Dehydrogenase Activity and Disrupt Cellular Metabolism
    2017
    Co-Authors: Azra Dad, Clara H. Jeong, Elizabeth D. Wagner, Michael J. Plewa
    Abstract:

    The disinfection of drinking water has been a major public health achievement. However, haloacetic Acids (HAAs), generated as byproducts of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown. In this study, we evaluated the effects of mono-, di-, and tri-HAAs on cellular GAPDH enzyme kinetics, cellular ATP levels, and pyruvate dehydrogenase complex (PDC) activity. Here, treatments conducted in Chinese hamster ovary (CHO) cells revealed differences among mono-, di-, and triHAAs in their molecular targets. The monoHAAs, iodoacetic Acid and Bromoacetic Acid, were the strongest inhibitors of GAPDH and greatly reduced cellular ATP levels. Chloroacetic Acid, diHAAs, and triHAAs were weaker inhibitors of GAPDH and some increased the levels of cellular ATP. HAAs also affected PDC activity, with most HAAs activating PDC. The primary finding of this work is that mono- versus multi-HAAs address different molecular targets, and the results are generally consistent with a model in which monoHAAs activate the PDC through GAPDH inhibition-mediated disruption in cellular metabolites, including altering ATP-to-ADP and NADH-to-NAD ratios. The monoHAA-mediated reduction in cellular metabolites results in accelerated PDC activity by way of metabolite-ratio-dependent PDC regulation. DiHAAs and triHAAs are weaker inhibitors of GAPDH, but many also increase cellular ATP levels, and we suggest that they increase PDC activity by inhibiting pyruvate dehydrogenase kinase

  • Energy of the Lowest Unoccupied Molecular Orbital, Thiol Reactivity, and Toxicity of Three Monobrominated Water Disinfection Byproducts
    2016
    Co-Authors: Justin A. Pals, Elizabeth D. Wagner, Michael J. Plewa
    Abstract:

    Disinfection of drinking water protects public health against waterborne pathogens. However, during disinfection, toxic disinfection byproducts (DBPs) are formed. Exposure to DBPs was associated with increased risk of bladder cancer in humans. DBPs are generated at concentrations below their carcinogenic potencies; it is unclear how exposure leads to adverse health outcomes. We used computational estimates of the energy of the lowest unoccupied molecular orbital (ELUMO) to predict thiol reactivity and additive toxicity among soft electrophile DBPs. Bromoacetic Acid (BAA) was identified as non-thiol-reactive, which was supported by in chemico and in vitro data. Bromoacetonitrile (BAN) and bromoacetamide (BAM) were thiol-reactive. Genotoxicity induced by these compounds was reduced by increasing the thiol pool with N-acetyl l-cysteine (NAC), while NAC had little effect on BAA. BAN and BAM shared depletion of glutathione (GSH) or cellular thiols as a molecular initiating event (MIE), whereas BAA induces toxicity through another pathway. Binary mixtures of BAM and BAN expressed a potentiating effect in genotoxicity. We found that soft electrophile DBPs could be an important predictor of common mechanism groups that demonstrated additive toxicity. In silico estimates of ELUMO could be used to identify the most relevant DBPs that are the forcing factors of the toxicity of finished drinking waters

  • In Vitro Cytotoxicity and Adaptive Stress Responses to Selected Haloacetic Acid and Halobenzoquinone Water Disinfection Byproducts
    2015
    Co-Authors: Erik Procházka, Michael J. Plewa, Beate I. Escher, Frederic D.l. Leusch
    Abstract:

    The process of disinfecting drinking water inadvertently leads to the formation of numerous disinfection byproducts (DBPs). Some of these are mutagenic, genotoxic, teratogenic, and cytotoxic, as well as potentially carcinogenic both in vivo and in vitro. We investigated the in vitro biological activity of five DBPs: three monohaloacetic Acids (monoHAAs) [chloroacetic Acid (CAA), Bromoacetic Acid (BAA), and iodoacetic Acid (IAA)] and two novel halobenzoquinones (HBQs) [2,6-dichloro-p-benzoquinone (DCBQ) and 2,6-dibromo-p-benzoquinone]. We focused particularly on cytotoxicity and induction of two adaptive stress response pathways: the oxidative stress responsive Nrf2/ARE and DNA-damage responsive p53 pathways. All five DBPs were cytotoxic to the Caco-2 cell line after a 4 h exposure, and all DBPs induced both of the adaptive stress response pathways, Nrf2/ARE and p53, in the micromolar range, as measured by two β-lactamase-based reporter gene assays. The decreasing order of potency for all three endpoints for the five DBPs was IAA ∼ BAA > DCBQ ∼ DBBQ > CAA. Induction of oxidative stress was previously proposed to be the molecular initiating event (MIE) for both classes of DBPs. However, comparing the levels of activation of the two pathways uncovered that the Nrf2/ARE pathway was the more sensitive endpoint for HAAs, whereas the p53 pathway was more sensitive in the case of HBQs. Therefore, the DNA damage-responsive p53 pathway may be an important piece of information to fill in a gap in the adverse outcome pathway framework for the assessment of HBQs. Finally, we cautiously compared the potential risk of the two novel HBQs using a benchmarking approach to that of the well-studied CAA, which suggested that their relative risk may be lower than that of BAA and IAA

Burtoloso, Antonio Carlos B. - One of the best experts on this subject based on the ideXlab platform.

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