Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells

Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Sassa, Akira [verfasserIn] Fukuda, Takayuki Ukai, Akiko Nakamura, Maki Takabe, Michihito Takamura-Enya, Takeji Honma, Masamitsu Yasui, Manabu

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Nucleotide excision repair XPC CSB Environmental mutagen Cytotoxicity TK6

Anmerkung:	© The Author(s) 2019

Übergeordnetes Werk:	Enthalten in: Genes and environment - [London] : BioMed Central, 2006, 41(2019), 1 vom: 16. Juli
Übergeordnetes Werk:	volume:41 ; year:2019 ; number:1 ; day:16 ; month:07

Links:	Volltext

DOI / URN:	10.1186/s41021-019-0130-y

Katalog-ID:	SPR038063913

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520			\|a Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants.
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author_variant	a s as t f tf a u au m n mn m t mt t t e tte m h mh m y my
matchkey_str	article:18807062:2019----::oprtvsuyfyooiefcsnuebevrnetleooissnxcncbeii
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allfields	10.1186/s41021-019-0130-y doi (DE-627)SPR038063913 (SPR)s41021-019-0130-y-e DE-627 ger DE-627 rakwb eng Sassa, Akira verfasserin aut Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. Nucleotide excision repair (dpeaa)DE-He213 XPC (dpeaa)DE-He213 CSB (dpeaa)DE-He213 Environmental mutagen (dpeaa)DE-He213 Cytotoxicity (dpeaa)DE-He213 TK6 (dpeaa)DE-He213 Fukuda, Takayuki aut Ukai, Akiko aut Nakamura, Maki aut Takabe, Michihito aut Takamura-Enya, Takeji aut Honma, Masamitsu aut Yasui, Manabu aut Enthalten in Genes and environment [London] : BioMed Central, 2006 41(2019), 1 vom: 16. Juli (DE-627)52422742X (DE-600)2269162-5 1880-7062 nnns volume:41 year:2019 number:1 day:16 month:07 https://dx.doi.org/10.1186/s41021-019-0130-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2019 1 16 07
spelling	10.1186/s41021-019-0130-y doi (DE-627)SPR038063913 (SPR)s41021-019-0130-y-e DE-627 ger DE-627 rakwb eng Sassa, Akira verfasserin aut Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. Nucleotide excision repair (dpeaa)DE-He213 XPC (dpeaa)DE-He213 CSB (dpeaa)DE-He213 Environmental mutagen (dpeaa)DE-He213 Cytotoxicity (dpeaa)DE-He213 TK6 (dpeaa)DE-He213 Fukuda, Takayuki aut Ukai, Akiko aut Nakamura, Maki aut Takabe, Michihito aut Takamura-Enya, Takeji aut Honma, Masamitsu aut Yasui, Manabu aut Enthalten in Genes and environment [London] : BioMed Central, 2006 41(2019), 1 vom: 16. Juli (DE-627)52422742X (DE-600)2269162-5 1880-7062 nnns volume:41 year:2019 number:1 day:16 month:07 https://dx.doi.org/10.1186/s41021-019-0130-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2019 1 16 07
allfields_unstemmed	10.1186/s41021-019-0130-y doi (DE-627)SPR038063913 (SPR)s41021-019-0130-y-e DE-627 ger DE-627 rakwb eng Sassa, Akira verfasserin aut Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. Nucleotide excision repair (dpeaa)DE-He213 XPC (dpeaa)DE-He213 CSB (dpeaa)DE-He213 Environmental mutagen (dpeaa)DE-He213 Cytotoxicity (dpeaa)DE-He213 TK6 (dpeaa)DE-He213 Fukuda, Takayuki aut Ukai, Akiko aut Nakamura, Maki aut Takabe, Michihito aut Takamura-Enya, Takeji aut Honma, Masamitsu aut Yasui, Manabu aut Enthalten in Genes and environment [London] : BioMed Central, 2006 41(2019), 1 vom: 16. Juli (DE-627)52422742X (DE-600)2269162-5 1880-7062 nnns volume:41 year:2019 number:1 day:16 month:07 https://dx.doi.org/10.1186/s41021-019-0130-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2019 1 16 07
allfieldsGer	10.1186/s41021-019-0130-y doi (DE-627)SPR038063913 (SPR)s41021-019-0130-y-e DE-627 ger DE-627 rakwb eng Sassa, Akira verfasserin aut Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. Nucleotide excision repair (dpeaa)DE-He213 XPC (dpeaa)DE-He213 CSB (dpeaa)DE-He213 Environmental mutagen (dpeaa)DE-He213 Cytotoxicity (dpeaa)DE-He213 TK6 (dpeaa)DE-He213 Fukuda, Takayuki aut Ukai, Akiko aut Nakamura, Maki aut Takabe, Michihito aut Takamura-Enya, Takeji aut Honma, Masamitsu aut Yasui, Manabu aut Enthalten in Genes and environment [London] : BioMed Central, 2006 41(2019), 1 vom: 16. Juli (DE-627)52422742X (DE-600)2269162-5 1880-7062 nnns volume:41 year:2019 number:1 day:16 month:07 https://dx.doi.org/10.1186/s41021-019-0130-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2019 1 16 07
allfieldsSound	10.1186/s41021-019-0130-y doi (DE-627)SPR038063913 (SPR)s41021-019-0130-y-e DE-627 ger DE-627 rakwb eng Sassa, Akira verfasserin aut Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2019 Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. Nucleotide excision repair (dpeaa)DE-He213 XPC (dpeaa)DE-He213 CSB (dpeaa)DE-He213 Environmental mutagen (dpeaa)DE-He213 Cytotoxicity (dpeaa)DE-He213 TK6 (dpeaa)DE-He213 Fukuda, Takayuki aut Ukai, Akiko aut Nakamura, Maki aut Takabe, Michihito aut Takamura-Enya, Takeji aut Honma, Masamitsu aut Yasui, Manabu aut Enthalten in Genes and environment [London] : BioMed Central, 2006 41(2019), 1 vom: 16. Juli (DE-627)52422742X (DE-600)2269162-5 1880-7062 nnns volume:41 year:2019 number:1 day:16 month:07 https://dx.doi.org/10.1186/s41021-019-0130-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2019 1 16 07
language	English
source	Enthalten in Genes and environment 41(2019), 1 vom: 16. Juli volume:41 year:2019 number:1 day:16 month:07
sourceStr	Enthalten in Genes and environment 41(2019), 1 vom: 16. Juli volume:41 year:2019 number:1 day:16 month:07
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Nucleotide excision repair XPC CSB Environmental mutagen Cytotoxicity TK6
isfreeaccess_bool	true
container_title	Genes and environment
authorswithroles_txt_mv	Sassa, Akira @@aut@@ Fukuda, Takayuki @@aut@@ Ukai, Akiko @@aut@@ Nakamura, Maki @@aut@@ Takabe, Michihito @@aut@@ Takamura-Enya, Takeji @@aut@@ Honma, Masamitsu @@aut@@ Yasui, Manabu @@aut@@
publishDateDaySort_date	2019-07-16T00:00:00Z
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id	SPR038063913
language_de	englisch
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To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. 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author	Sassa, Akira
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topic_title	Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells Nucleotide excision repair (dpeaa)DE-He213 XPC (dpeaa)DE-He213 CSB (dpeaa)DE-He213 Environmental mutagen (dpeaa)DE-He213 Cytotoxicity (dpeaa)DE-He213 TK6 (dpeaa)DE-He213
topic	misc Nucleotide excision repair misc XPC misc CSB misc Environmental mutagen misc Cytotoxicity misc TK6
topic_unstemmed	misc Nucleotide excision repair misc XPC misc CSB misc Environmental mutagen misc Cytotoxicity misc TK6
topic_browse	misc Nucleotide excision repair misc XPC misc CSB misc Environmental mutagen misc Cytotoxicity misc TK6
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells
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title_full	Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells
author_sort	Sassa, Akira
journal	Genes and environment
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lang_code	eng
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author_browse	Sassa, Akira Fukuda, Takayuki Ukai, Akiko Nakamura, Maki Takabe, Michihito Takamura-Enya, Takeji Honma, Masamitsu Yasui, Manabu
container_volume	41
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author-letter	Sassa, Akira
doi_str_mv	10.1186/s41021-019-0130-y
title_sort	comparative study of cytotoxic effects induced by environmental genotoxins using xpc- and csb-deficient human lymphoblastoid tk6 cells
title_auth	Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells
abstract	Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. © The Author(s) 2019
abstractGer	Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. © The Author(s) 2019
abstract_unstemmed	Background The human genome is constantly exposed to numerous environmental genotoxicants. To prevent the detrimental consequences induced by the expansion of damaged cells, cellular protective systems such as nucleotide excision repair (NER) exist and serve as a primary pathway for repairing the various helix-distorting DNA adducts induced by genotoxic agents. NER is further divided into two sub-pathways, namely, global genomic NER (GG-NER) and transcription-coupled NER (TC-NER). Both NER sub-pathways are reportedly involved in the damage response elicited by exposure to genotoxins. However, how disruption of these sub-pathways impacts the toxicity of different types of environmental mutagens in human cells is not well understood. Results To evaluate the role of NER sub-pathways on the cytotoxic effects of mutagens, we disrupted XPC and CSB to selectively inactivate GG-NER and TC-NER, respectively, in human lymphoblastoid TK6 cells, a standard cell line used in genotoxicity studies. Using these cells, we then comparatively assessed their respective sensitivities to representative genotoxic agents, including ultraviolet C (UVC) light, benzo [a] pyrene (B(a)P), 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), γ-ray, and 2-acetylaminofluorene (2-AAF). CSB−/− cells exhibited a hyper-sensitivity to UVC, B(a)P, and MeIQx. On the other hand, XPC−/− cells were highly sensitive to UVC, but not to B(a)P and MeIQx, compared with wild-type cells. In contrast with other genotoxins, the sensitivity of XPC−/− cells against PhIP was significantly higher than CSB−/− cells. The toxicity of γ-ray and 2-AAF was not enhanced by disruption of either XPC or CSB in the cells. Conclusions Based on our findings, genetically modified TK6 cells appear to be a useful tool for elucidating the detailed roles of the various repair factors that exist to combat genotoxic agents, and should contribute to the improved risk assessment of environmental chemical contaminants. © The Author(s) 2019
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title_short	Comparative study of cytotoxic effects induced by environmental genotoxins using XPC- and CSB-deficient human lymphoblastoid TK6 cells
url	https://dx.doi.org/10.1186/s41021-019-0130-y
remote_bool	true
author2	Fukuda, Takayuki Ukai, Akiko Nakamura, Maki Takabe, Michihito Takamura-Enya, Takeji Honma, Masamitsu Yasui, Manabu
author2Str	Fukuda, Takayuki Ukai, Akiko Nakamura, Maki Takabe, Michihito Takamura-Enya, Takeji Honma, Masamitsu Yasui, Manabu
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