Genotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells

Abstract The human genome is persistently exposed to damage caused by xenobiotics, therefore the assessment of genotoxicity of substances having a direct contact with humans is of importance. Phthalates are commonly used in industrial applications. Widespread exposure to phthalates has been evidence...

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Autores principales:	Paulina Sicińska, Katarzyna Mokra, Katarzyna Wozniak, Jaromir Michałowicz, Bożena Bukowska
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3a3a3989fd704977bc46a940b672f019
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spelling	oai:doaj.org-article:3a3a3989fd704977bc46a940b672f0192021-12-02T15:23:39ZGenotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells10.1038/s41598-020-79932-52045-2322https://doaj.org/article/3a3a3989fd704977bc46a940b672f0192021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79932-5https://doaj.org/toc/2045-2322Abstract The human genome is persistently exposed to damage caused by xenobiotics, therefore the assessment of genotoxicity of substances having a direct contact with humans is of importance. Phthalates are commonly used in industrial applications. Widespread exposure to phthalates has been evidenced by their presence in human body fluids. We have assessed the genotoxic potential of selected phthalates and mechanism of their action in human peripheral blood mononuclear cells (PBMCs). Studied cells were incubated with di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP) and their metabolites: mono-n-butylphthalate (MBP), mono-benzylphthalate (MBzP) in the concentrations range of 0.1–10 µg/mL for 24 h. Analyzed compounds induced DNA single and double strand-breaks (DBP and BBP ≥ 0.5 µg/mL, MBP and MBzP ≥ 1 µg/mL) and more strongly oxidized purines than pyrimidines. None of the compounds examined was capable of creating adducts with DNA. All studied phthalates caused an increase of total ROS level, while hydroxyl radical was generated mostly by DBP and BBP. PBMCs exposed to DBP and BBP could not completely repair DNA strand-breaks during 120 min of postincubation, in opposite to damage caused by their metabolites, MBP and MBzP. We have concluded that parent phthalates: DBP and BBP caused more pronounced DNA damage compared to their metabolites.Paulina SicińskaKatarzyna MokraKatarzyna WozniakJaromir MichałowiczBożena BukowskaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paulina Sicińska Katarzyna Mokra Katarzyna Wozniak Jaromir Michałowicz Bożena Bukowska Genotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells
description	Abstract The human genome is persistently exposed to damage caused by xenobiotics, therefore the assessment of genotoxicity of substances having a direct contact with humans is of importance. Phthalates are commonly used in industrial applications. Widespread exposure to phthalates has been evidenced by their presence in human body fluids. We have assessed the genotoxic potential of selected phthalates and mechanism of their action in human peripheral blood mononuclear cells (PBMCs). Studied cells were incubated with di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP) and their metabolites: mono-n-butylphthalate (MBP), mono-benzylphthalate (MBzP) in the concentrations range of 0.1–10 µg/mL for 24 h. Analyzed compounds induced DNA single and double strand-breaks (DBP and BBP ≥ 0.5 µg/mL, MBP and MBzP ≥ 1 µg/mL) and more strongly oxidized purines than pyrimidines. None of the compounds examined was capable of creating adducts with DNA. All studied phthalates caused an increase of total ROS level, while hydroxyl radical was generated mostly by DBP and BBP. PBMCs exposed to DBP and BBP could not completely repair DNA strand-breaks during 120 min of postincubation, in opposite to damage caused by their metabolites, MBP and MBzP. We have concluded that parent phthalates: DBP and BBP caused more pronounced DNA damage compared to their metabolites.
format	article
author	Paulina Sicińska Katarzyna Mokra Katarzyna Wozniak Jaromir Michałowicz Bożena Bukowska
author_facet	Paulina Sicińska Katarzyna Mokra Katarzyna Wozniak Jaromir Michałowicz Bożena Bukowska
author_sort	Paulina Sicińska
title	Genotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells
title_short	Genotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells
title_full	Genotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells
title_fullStr	Genotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells
title_full_unstemmed	Genotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells
title_sort	genotoxic risk assessment and mechanism of dna damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3a3a3989fd704977bc46a940b672f019
work_keys_str_mv	AT paulinasicinska genotoxicriskassessmentandmechanismofdnadamageinducedbyphthalatesandtheirmetabolitesinhumanperipheralbloodmononuclearcells AT katarzynamokra genotoxicriskassessmentandmechanismofdnadamageinducedbyphthalatesandtheirmetabolitesinhumanperipheralbloodmononuclearcells AT katarzynawozniak genotoxicriskassessmentandmechanismofdnadamageinducedbyphthalatesandtheirmetabolitesinhumanperipheralbloodmononuclearcells AT jaromirmichałowicz genotoxicriskassessmentandmechanismofdnadamageinducedbyphthalatesandtheirmetabolitesinhumanperipheralbloodmononuclearcells AT bozenabukowska genotoxicriskassessmentandmechanismofdnadamageinducedbyphthalatesandtheirmetabolitesinhumanperipheralbloodmononuclearcells
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Genotoxic risk assessment and mechanism of DNA damage induced by phthalates and their metabolites in human peripheral blood mononuclear cells

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