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 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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Sicińska P,Mokra K,Wozniak K,Michałowicz J,Bukowska B

doi

10.1038/s41598-020-79932-5

subject

Has Abstract

pub_date

2021-01-18 00:00:00

pages

1658

issue

1

issn

2045-2322

pii

10.1038/s41598-020-79932-5

journal_volume

11

pub_type

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