The Experts below are selected from a list of 31632 Experts worldwide ranked by ideXlab platform
Jan Kapuscinski - One of the best experts on this subject based on the ideXlab platform.
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the modulation by xanthines of the dna Damaging Effect of polycyclic aromatic agents part ii the stacking complexes of caffeine with doxorubicin and mitoxantrone
Biochemical Pharmacology, 2002Co-Authors: Jacek Piosik, Malgorzata Zdunek, Jan KapuscinskiAbstract:Recently accumulated statistical data indicate the protective Effect of caffeine consumption against several types of cancer diseases. There are also reports about protective Effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations of this phenomenon is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine. In the accompanying paper [Kapuscinski et al., this issue] we provide evidence (flow cytometry and the cell cycle analysis) that the cytostatic Effects of caffeine (CAF) on two DNA alkylating agents, which do not require the biological activation, depend on their ability to form stacking (pi-pi) complexes. In this study, we use physicochemical techniques (computer aided light absorption and microcalorimetry), and molecular modeling to examine previously published qualitative data. This is published both by our and other group's data, indicates that CAF is able to modify the cytotoxic and/or cytostatic action of the two well known antitumor drugs doxorubicin (DOX) and mitoxantrone (MIT). To obtain the quantitative results from the experimental data we used the statistical-thermodynamical model of mixed aggregation, to find the association constants K(AC) of the CAF-drug interaction (128+/-10 and 356+/-21M(-1) for DOX-CAF and MIT-CAF complex formation, respectively). In addition, the favorable enthalpy change of CAF-MIT (DeltaH=-11.3kcal/mol) was measured by microcalorimetry titration. The molecular modeling (semi-empirical and force field method) allowed us to obtain the geometry of these complexes, which indicated the favorable energy (DeltaE) of complex formation of the protonated drug's molecules in aqueous environment (-7.4 and -8.7kcal/mol for DOX-CAF.5H(2)O and MIT-CAF.8H(2)O complex, respectively). The molecular modeling calculation indicates the existence of CAF-drug complexes in which the MIT molecules are intercalated between two CAF molecules (DeltaE=-29.9kcal/mol). These results indicate that the attenuating Effect of caffeine on cytotoxic or mutagenic Effects of some polycyclic aromatic mutagens cannot be the result of metabolic activation in the cells, but simply is the physicochemical process of the sequestering of aromatic molecules (e.g. carcinogens or mutagens) by formation of the stacking complexes. The caffeine may then act as the "interceptor" of potential carcinogens (especially in the upper part of digesting track) where its concentration can reach the mM level). There is, however, no indication, both, in the literature or from our experiments, that the xanthines can reverse the damage to nucleic acids at the point when the damage to DNA has already occurred.
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the modulation of the dna Damaging Effect of polycyclic aromatic agents by xanthines part i reduction of cytostatic Effects of quinacrine mustard by caffeine
Biochemical Pharmacology, 2002Co-Authors: Jan Kapuscinski, Jacek Piosik, Malgorzata Zdunek, Barbara Ardelt, Zbigniew DarzynkiewiczAbstract:Abstract Recently, accumulated statistical data indicate the protective Effect of caffeine consumption against several types of cancer diseases. There are also reports about protective Effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine. However, there is also numerous data indicating reverse Effect on cytotoxicity of anticancer drugs that inhibit the action of topoisomerase I (e.g. Camptothecin or Topotecan) and topoisomerase II inhibitors (e.g. Doxorubicin, Mitoxantrone or mAMSA). In this work we tested the hypothesis that the caffeine protective Effect is the result of sequestering of aromatic mutagens by formation of stacking (π–π) complexes. As the models for the study we have chosen two well-known mutagens, that do not require metabolical activation: quinacrine mustard(QM, aromatic, heterocyclic nitrogen mustard) and mechlorethamine (NM2, aliphatic nitrogen mustard). The flow cytometry study of these agents’ action on the cell cycle of HL-60 cells indicated that caffeine prevents the cytotoxic action of QM, but not that of NM2. The formations of stacking complexes of QM with caffeine were confirmed by light absorption, calorimetric measurements and by molecular modeling calculation. Using the statistical thermodynamics calculations we calculated the “neighborhood” association constant (KAC=59±2 M−1) and enthalpy change ( Δ H 0′ =−116 cal mol −1 ); the favorable entropy change of complex formation ( Δ S 0′ =7.72 cal mol −1 K −1 , due to release of several water molecules, associated with components in the process of complex formation). The Gibbs’ free energy change of QM–CAF formation is Δ G 0′ =−2.41 kcal mol −1 . We were unable to detect any interaction between NM2 and caffeine either by spectroscopic or calorimetric measurement. In order to establish, whether the intercalation of QM plays any role in cytotoxic Effect we tested, as a control, non-alkylatiatig, but also intercalating QM derivative—quinacrine (Q). The later had no cytostatic Effect on HL-60 cell even at there order of higher concentration than QM or NM2 but, similar to QM forms (which we demonstrated) stacking complexes with caffeine (KAC=75±3 M−1). These results strongly indicate, that the attenuating Effect of caffeine on cytotoxic or mutagenic Effects of some mutagens, is not the results of metabolic processes in the cells, but simply the physicochemical process of sequestering of aromatic molecules (potential carcinogens or mutagens) by formation of stacking complexes with them. The caffeine may then act as the “interceptor” of potential carcinogens (especially in the upper part of digesting track where its concentration can reach the concentration of mM level). There is, however, no indication either in the literature or in our experiments that xanthines can reverse the damage to nucleic acids when the damage to DNA has already occurred.
Wang Zijian - One of the best experts on this subject based on the ideXlab platform.
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application of the sos umu test and high content in vitro micronucleus test to determine genotoxicity and cytotoxicity of nine benzothiazoles
Journal of Applied Toxicology, 2014Co-Authors: Jiang Weiwei, Ma Mei, Rao Kaifeng, Wang ZijianAbstract:Benzothiazole and benzothiazole derivatives (BTs) have been detected in various environmental matrices as well as in human beings, but little is currently available regarding their toxicities. In our study, genotoxicities of nine BTs (benzothiazole [BT], 2-chlorobenzothiazole [CBT], 2-bromobenzothiazole [BrBT], 2-fluorobenzothiazole [FBT], 2-methylbenzothiazole [MeBT], 2-mercaptobenzothiazole [MBT], 2-aminobenzothiazole [ABT], 2-hydroxy-benzothiazole [OHBT] and 2-methythiobenzothiazole [MTBT]) are comprehensively evaluated by the SOS/umu test using the bacterial Salmonella typhimurium TA1535/pSK1002 for DNA-Damaging Effect and the high content in vitro micronucleus test using two human carcinoma cells (MGC-803 and A549) for chromosome-Damaging Effect. The cytotoxicity of BTs on both bacteria and two human cells was also evaluated. Except for the cytotoxic Effect of MBT on MGC-803 and A549, the other tested BTs showed more than 50% cytotoxicity at their highest concentrations in a dose-dependent manner, and their LC50s ranged from 19 (MBT in bacteria) to 270 mg l(-1) (CBT in A549). Activation and inactivation were observed for specific BTs after metabolism. On the other hand, no evidence of genotoxicity was obtained for BT, FBT and MBT, and DNA damage was induced by ABT, OHBT, BrBT and MTBT in MGC-803, by MeBT in A549 and by CBT in both cells. Through quantitative structure-activity relationship analysis, two structure alerts for chemical genotoxicity, including heterocyclic amine and hacceptor-path3-hacceptor are present in ABT and OHBT respectively; however, the underlying mechanisms still need further evaluation. Copyright (c) 2014 John Wiley a Sons, Ltd. Cytotoxicity of BTs in both bacterial Salmonella typhimurium TA1535/pSK1002, MGC-803 and A549 cells was observed in a dose-dependent manner, and activation and inactivation were found for specific BTs after metabolism. Six of nine BTs were found to be genotoxic to either bacteria or cells or both, and structure alerts including heterocyclic amine and hacceptor-path3-hacceptor may contribute to the underlying genotoxic mechanism for 2-Aminobenzothiazole and 2-Hydroxy-benzothiazole respectively.
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assessing of genotoxicity of 16 centralized source waters in china by means of the sos umu assay and the micronucleus test initial identification of the potential genotoxicants by use of a gc ms method and the qsar toolbox 3 0
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2014Co-Authors: Yan Ye, Jiang Weiwei, Wang Zijian, Li Na, Wang Donghong, Rao KaifengAbstract:Only few studies were conducted to assess genotoxicity of centralized source waters in China and almost none of them dealt with the causal relationship between the genotoxic Effect and genotoxicants. In this work, 16 centralized source waters in China were sampled from five river systems and genotoxicity of their organic extracts was assessed by use of the SOS/umu test for DNA-Damaging Effect and the miniaturized flow cytometry-based micronucleus (MN) test for chromosome-Damaging Effect. In addition, initial identification of potential genotoxicants for the six samples from the Yangtze River was done with a GC/MS method and the QSAR toolbox 3.0. The results demonstrate that eight samples showed both indirect and direct DNA-Damaging Effects, another four samples showed only indirect DNA-Damaging Effects, while chromosome-Damaging Effects were found for 14 out of the 16 samples, in which aneugenic and clastogenic modes of action were found for 4 and 10 samples, respectively. Both direct/indirect DNA-Damaging Effects and chromosome-Damaging Effects were induced by the six Yangtze River samples, and the existing different types of genotoxicant confirmed the results. Furthermore, o-phenylphenol was initially identified as the major cause for the DNA-Damaging Effects while PAHs, pesticides, phenol and anthraquinone were identified as ubiquitous chromosome-Damaging agents among these samples. In conclusion, a combination of the SOS/umu test and the miniaturized flow cytometry-based MN test to detect both DNA-Damaging and chromosome-Damaging Effects could be used as a comprehensive genotoxicity assessment tool for the evaluation and classification of genotoxicity of complex mixtures, and potential genotoxicants can be initially identified with additional information from chemical analysis and the QSAR toolbox.
Rao Kaifeng - One of the best experts on this subject based on the ideXlab platform.
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application of the sos umu test and high content in vitro micronucleus test to determine genotoxicity and cytotoxicity of nine benzothiazoles
Journal of Applied Toxicology, 2014Co-Authors: Jiang Weiwei, Ma Mei, Rao Kaifeng, Wang ZijianAbstract:Benzothiazole and benzothiazole derivatives (BTs) have been detected in various environmental matrices as well as in human beings, but little is currently available regarding their toxicities. In our study, genotoxicities of nine BTs (benzothiazole [BT], 2-chlorobenzothiazole [CBT], 2-bromobenzothiazole [BrBT], 2-fluorobenzothiazole [FBT], 2-methylbenzothiazole [MeBT], 2-mercaptobenzothiazole [MBT], 2-aminobenzothiazole [ABT], 2-hydroxy-benzothiazole [OHBT] and 2-methythiobenzothiazole [MTBT]) are comprehensively evaluated by the SOS/umu test using the bacterial Salmonella typhimurium TA1535/pSK1002 for DNA-Damaging Effect and the high content in vitro micronucleus test using two human carcinoma cells (MGC-803 and A549) for chromosome-Damaging Effect. The cytotoxicity of BTs on both bacteria and two human cells was also evaluated. Except for the cytotoxic Effect of MBT on MGC-803 and A549, the other tested BTs showed more than 50% cytotoxicity at their highest concentrations in a dose-dependent manner, and their LC50s ranged from 19 (MBT in bacteria) to 270 mg l(-1) (CBT in A549). Activation and inactivation were observed for specific BTs after metabolism. On the other hand, no evidence of genotoxicity was obtained for BT, FBT and MBT, and DNA damage was induced by ABT, OHBT, BrBT and MTBT in MGC-803, by MeBT in A549 and by CBT in both cells. Through quantitative structure-activity relationship analysis, two structure alerts for chemical genotoxicity, including heterocyclic amine and hacceptor-path3-hacceptor are present in ABT and OHBT respectively; however, the underlying mechanisms still need further evaluation. Copyright (c) 2014 John Wiley a Sons, Ltd. Cytotoxicity of BTs in both bacterial Salmonella typhimurium TA1535/pSK1002, MGC-803 and A549 cells was observed in a dose-dependent manner, and activation and inactivation were found for specific BTs after metabolism. Six of nine BTs were found to be genotoxic to either bacteria or cells or both, and structure alerts including heterocyclic amine and hacceptor-path3-hacceptor may contribute to the underlying genotoxic mechanism for 2-Aminobenzothiazole and 2-Hydroxy-benzothiazole respectively.
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assessing of genotoxicity of 16 centralized source waters in china by means of the sos umu assay and the micronucleus test initial identification of the potential genotoxicants by use of a gc ms method and the qsar toolbox 3 0
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2014Co-Authors: Yan Ye, Jiang Weiwei, Wang Zijian, Li Na, Wang Donghong, Rao KaifengAbstract:Only few studies were conducted to assess genotoxicity of centralized source waters in China and almost none of them dealt with the causal relationship between the genotoxic Effect and genotoxicants. In this work, 16 centralized source waters in China were sampled from five river systems and genotoxicity of their organic extracts was assessed by use of the SOS/umu test for DNA-Damaging Effect and the miniaturized flow cytometry-based micronucleus (MN) test for chromosome-Damaging Effect. In addition, initial identification of potential genotoxicants for the six samples from the Yangtze River was done with a GC/MS method and the QSAR toolbox 3.0. The results demonstrate that eight samples showed both indirect and direct DNA-Damaging Effects, another four samples showed only indirect DNA-Damaging Effects, while chromosome-Damaging Effects were found for 14 out of the 16 samples, in which aneugenic and clastogenic modes of action were found for 4 and 10 samples, respectively. Both direct/indirect DNA-Damaging Effects and chromosome-Damaging Effects were induced by the six Yangtze River samples, and the existing different types of genotoxicant confirmed the results. Furthermore, o-phenylphenol was initially identified as the major cause for the DNA-Damaging Effects while PAHs, pesticides, phenol and anthraquinone were identified as ubiquitous chromosome-Damaging agents among these samples. In conclusion, a combination of the SOS/umu test and the miniaturized flow cytometry-based MN test to detect both DNA-Damaging and chromosome-Damaging Effects could be used as a comprehensive genotoxicity assessment tool for the evaluation and classification of genotoxicity of complex mixtures, and potential genotoxicants can be initially identified with additional information from chemical analysis and the QSAR toolbox.
Jacek Piosik - One of the best experts on this subject based on the ideXlab platform.
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the modulation by xanthines of the dna Damaging Effect of polycyclic aromatic agents part ii the stacking complexes of caffeine with doxorubicin and mitoxantrone
Biochemical Pharmacology, 2002Co-Authors: Jacek Piosik, Malgorzata Zdunek, Jan KapuscinskiAbstract:Recently accumulated statistical data indicate the protective Effect of caffeine consumption against several types of cancer diseases. There are also reports about protective Effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations of this phenomenon is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine. In the accompanying paper [Kapuscinski et al., this issue] we provide evidence (flow cytometry and the cell cycle analysis) that the cytostatic Effects of caffeine (CAF) on two DNA alkylating agents, which do not require the biological activation, depend on their ability to form stacking (pi-pi) complexes. In this study, we use physicochemical techniques (computer aided light absorption and microcalorimetry), and molecular modeling to examine previously published qualitative data. This is published both by our and other group's data, indicates that CAF is able to modify the cytotoxic and/or cytostatic action of the two well known antitumor drugs doxorubicin (DOX) and mitoxantrone (MIT). To obtain the quantitative results from the experimental data we used the statistical-thermodynamical model of mixed aggregation, to find the association constants K(AC) of the CAF-drug interaction (128+/-10 and 356+/-21M(-1) for DOX-CAF and MIT-CAF complex formation, respectively). In addition, the favorable enthalpy change of CAF-MIT (DeltaH=-11.3kcal/mol) was measured by microcalorimetry titration. The molecular modeling (semi-empirical and force field method) allowed us to obtain the geometry of these complexes, which indicated the favorable energy (DeltaE) of complex formation of the protonated drug's molecules in aqueous environment (-7.4 and -8.7kcal/mol for DOX-CAF.5H(2)O and MIT-CAF.8H(2)O complex, respectively). The molecular modeling calculation indicates the existence of CAF-drug complexes in which the MIT molecules are intercalated between two CAF molecules (DeltaE=-29.9kcal/mol). These results indicate that the attenuating Effect of caffeine on cytotoxic or mutagenic Effects of some polycyclic aromatic mutagens cannot be the result of metabolic activation in the cells, but simply is the physicochemical process of the sequestering of aromatic molecules (e.g. carcinogens or mutagens) by formation of the stacking complexes. The caffeine may then act as the "interceptor" of potential carcinogens (especially in the upper part of digesting track) where its concentration can reach the mM level). There is, however, no indication, both, in the literature or from our experiments, that the xanthines can reverse the damage to nucleic acids at the point when the damage to DNA has already occurred.
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the modulation of the dna Damaging Effect of polycyclic aromatic agents by xanthines part i reduction of cytostatic Effects of quinacrine mustard by caffeine
Biochemical Pharmacology, 2002Co-Authors: Jan Kapuscinski, Jacek Piosik, Malgorzata Zdunek, Barbara Ardelt, Zbigniew DarzynkiewiczAbstract:Abstract Recently, accumulated statistical data indicate the protective Effect of caffeine consumption against several types of cancer diseases. There are also reports about protective Effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine. However, there is also numerous data indicating reverse Effect on cytotoxicity of anticancer drugs that inhibit the action of topoisomerase I (e.g. Camptothecin or Topotecan) and topoisomerase II inhibitors (e.g. Doxorubicin, Mitoxantrone or mAMSA). In this work we tested the hypothesis that the caffeine protective Effect is the result of sequestering of aromatic mutagens by formation of stacking (π–π) complexes. As the models for the study we have chosen two well-known mutagens, that do not require metabolical activation: quinacrine mustard(QM, aromatic, heterocyclic nitrogen mustard) and mechlorethamine (NM2, aliphatic nitrogen mustard). The flow cytometry study of these agents’ action on the cell cycle of HL-60 cells indicated that caffeine prevents the cytotoxic action of QM, but not that of NM2. The formations of stacking complexes of QM with caffeine were confirmed by light absorption, calorimetric measurements and by molecular modeling calculation. Using the statistical thermodynamics calculations we calculated the “neighborhood” association constant (KAC=59±2 M−1) and enthalpy change ( Δ H 0′ =−116 cal mol −1 ); the favorable entropy change of complex formation ( Δ S 0′ =7.72 cal mol −1 K −1 , due to release of several water molecules, associated with components in the process of complex formation). The Gibbs’ free energy change of QM–CAF formation is Δ G 0′ =−2.41 kcal mol −1 . We were unable to detect any interaction between NM2 and caffeine either by spectroscopic or calorimetric measurement. In order to establish, whether the intercalation of QM plays any role in cytotoxic Effect we tested, as a control, non-alkylatiatig, but also intercalating QM derivative—quinacrine (Q). The later had no cytostatic Effect on HL-60 cell even at there order of higher concentration than QM or NM2 but, similar to QM forms (which we demonstrated) stacking complexes with caffeine (KAC=75±3 M−1). These results strongly indicate, that the attenuating Effect of caffeine on cytotoxic or mutagenic Effects of some mutagens, is not the results of metabolic processes in the cells, but simply the physicochemical process of sequestering of aromatic molecules (potential carcinogens or mutagens) by formation of stacking complexes with them. The caffeine may then act as the “interceptor” of potential carcinogens (especially in the upper part of digesting track where its concentration can reach the concentration of mM level). There is, however, no indication either in the literature or in our experiments that xanthines can reverse the damage to nucleic acids when the damage to DNA has already occurred.
Jiang Weiwei - One of the best experts on this subject based on the ideXlab platform.
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application of the sos umu test and high content in vitro micronucleus test to determine genotoxicity and cytotoxicity of nine benzothiazoles
Journal of Applied Toxicology, 2014Co-Authors: Jiang Weiwei, Ma Mei, Rao Kaifeng, Wang ZijianAbstract:Benzothiazole and benzothiazole derivatives (BTs) have been detected in various environmental matrices as well as in human beings, but little is currently available regarding their toxicities. In our study, genotoxicities of nine BTs (benzothiazole [BT], 2-chlorobenzothiazole [CBT], 2-bromobenzothiazole [BrBT], 2-fluorobenzothiazole [FBT], 2-methylbenzothiazole [MeBT], 2-mercaptobenzothiazole [MBT], 2-aminobenzothiazole [ABT], 2-hydroxy-benzothiazole [OHBT] and 2-methythiobenzothiazole [MTBT]) are comprehensively evaluated by the SOS/umu test using the bacterial Salmonella typhimurium TA1535/pSK1002 for DNA-Damaging Effect and the high content in vitro micronucleus test using two human carcinoma cells (MGC-803 and A549) for chromosome-Damaging Effect. The cytotoxicity of BTs on both bacteria and two human cells was also evaluated. Except for the cytotoxic Effect of MBT on MGC-803 and A549, the other tested BTs showed more than 50% cytotoxicity at their highest concentrations in a dose-dependent manner, and their LC50s ranged from 19 (MBT in bacteria) to 270 mg l(-1) (CBT in A549). Activation and inactivation were observed for specific BTs after metabolism. On the other hand, no evidence of genotoxicity was obtained for BT, FBT and MBT, and DNA damage was induced by ABT, OHBT, BrBT and MTBT in MGC-803, by MeBT in A549 and by CBT in both cells. Through quantitative structure-activity relationship analysis, two structure alerts for chemical genotoxicity, including heterocyclic amine and hacceptor-path3-hacceptor are present in ABT and OHBT respectively; however, the underlying mechanisms still need further evaluation. Copyright (c) 2014 John Wiley a Sons, Ltd. Cytotoxicity of BTs in both bacterial Salmonella typhimurium TA1535/pSK1002, MGC-803 and A549 cells was observed in a dose-dependent manner, and activation and inactivation were found for specific BTs after metabolism. Six of nine BTs were found to be genotoxic to either bacteria or cells or both, and structure alerts including heterocyclic amine and hacceptor-path3-hacceptor may contribute to the underlying genotoxic mechanism for 2-Aminobenzothiazole and 2-Hydroxy-benzothiazole respectively.
-
assessing of genotoxicity of 16 centralized source waters in china by means of the sos umu assay and the micronucleus test initial identification of the potential genotoxicants by use of a gc ms method and the qsar toolbox 3 0
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2014Co-Authors: Yan Ye, Jiang Weiwei, Wang Zijian, Li Na, Wang Donghong, Rao KaifengAbstract:Only few studies were conducted to assess genotoxicity of centralized source waters in China and almost none of them dealt with the causal relationship between the genotoxic Effect and genotoxicants. In this work, 16 centralized source waters in China were sampled from five river systems and genotoxicity of their organic extracts was assessed by use of the SOS/umu test for DNA-Damaging Effect and the miniaturized flow cytometry-based micronucleus (MN) test for chromosome-Damaging Effect. In addition, initial identification of potential genotoxicants for the six samples from the Yangtze River was done with a GC/MS method and the QSAR toolbox 3.0. The results demonstrate that eight samples showed both indirect and direct DNA-Damaging Effects, another four samples showed only indirect DNA-Damaging Effects, while chromosome-Damaging Effects were found for 14 out of the 16 samples, in which aneugenic and clastogenic modes of action were found for 4 and 10 samples, respectively. Both direct/indirect DNA-Damaging Effects and chromosome-Damaging Effects were induced by the six Yangtze River samples, and the existing different types of genotoxicant confirmed the results. Furthermore, o-phenylphenol was initially identified as the major cause for the DNA-Damaging Effects while PAHs, pesticides, phenol and anthraquinone were identified as ubiquitous chromosome-Damaging agents among these samples. In conclusion, a combination of the SOS/umu test and the miniaturized flow cytometry-based MN test to detect both DNA-Damaging and chromosome-Damaging Effects could be used as a comprehensive genotoxicity assessment tool for the evaluation and classification of genotoxicity of complex mixtures, and potential genotoxicants can be initially identified with additional information from chemical analysis and the QSAR toolbox.
