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.
Highlights
The human genome is persistently exposed to damage caused by xenobiotics, the assessment of genotoxicity of substances having a direct contact with humans is of importance
Significant increase in DNA damage was induced in peripheral blood mononuclear cells (PBMCs) by di-n-butyl phthalate (DBP) and butylbenzyl phthalate (BBP) starting from the concentration of 0.5 μg/mL and the tail intensity (TI) was evaluated to be 7.2% and 6%, respectively
It has been shown that the tested phthalates in the concentrations range from 0.1 to 10 μg/mL after 24 h of incubation with PBMCs caused DNA damage (DBP and BBP ≥ 0.5 μg/mL, MBP and MBzP ≥ 1 μg/mL)
Summary
The human genome is persistently exposed to damage caused by xenobiotics, the assessment of genotoxicity of substances having a direct contact with humans is of importance. 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. According to the EU Commission Directive 2018/2005, four phthalates, including DEHP (di(2-ethylhexyl) phthalate), DBP, BBP and DIBP (diisobutyl phthalate), are considered to be harmful for human reproduction (category 1B). Those phthalates must not be contained in products intended for children in the amount of over 0.1% (single nor sum of all contained phthalates) of the overall weight of the p roduct[13]. It is estimated that food-related exposure to Scientific Reports | (2021) 11:1658
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