Genotoxic Mechanism of Action of TBBPA, TBBPS and Selected Bromophenols in Human Peripheral Blood Mononuclear Cells

Abstract

Bromophenolic flame retardants (BFRs) are a large group of synthetic substances used in the industry in order to reduce the flammability of synthetic materials used in electrical and electronic devices, textiles, furniture and other everyday products. The presence of BFRs has been documented in the environment, food, drinking water, inhaled dust and the human body. Due to the widespread exposure of the general population to BFRs and insufficient knowledge on their toxic action, including genotoxic potential, we have compared the effect of tetrabromobisphenol A (TBBPA), tetrabromobisphenol S (TBBPS), 2,4,6,-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) on DNA damage in human peripheral blood mononuclear cells (PBMCs) (playing a crucial role in the immune system) as well as examined underlying mechanism of action of these substances. The cells were incubated for 24 h with studied compounds in the concentrations ranging from 0.01 to 10 µg/mL. The study has shown that examined BFRs induced single and, to a lesser extent, double strand-breaks formation and caused oxidative damage to pyrimidines, and particularly to purines in the incubated cells. PBMCs efficiently repaired the DNA strand-breaks induced by BFRs, but they were unable to remove completely damaged DNA (except cells treated with TBBPS). The greatest changes in the above-mentioned parameters were observed in cells incubated with TBBPA, while the smallest in PBMCs treated with TBBPS. The results have also revealed that tested compounds do not form adducts with DNA in PBMCs, while the observed changes were the most probably induced by indirect DNA-damaging agents, such as ROS and other reactive species.

Apoptosis-Inducing Potential of Selected Bromophenolic Flame Retardants 2,4,6-Tribromophenol and Pentabromophenol in Human Peripheral Blood Mononuclear Cells

“…An increase in reactive oxygen species (ROS) formation (as observed in our previous study on the prooxidative effects of 2,4,6-TBP and PBP on human PBMCs [34]) and raised cytosolic calcium ion level impair electrolyte transport across the mitochondrial membrane, causing the opening of the mitochondrial permeability transition pores (PTPs), which results in the release of various proapoptotic molecules, such as apoptosis-inducing factor (AIF), cytochrome c, and procaspase-9, into the cytosol [36]. As a consequence, an apoptosome is formed, which leads to caspase-9 activation, and subsequently to the initiation of the intrinsic (mitochondrial) pathway of apoptosis.…”

“…In red blood cells, 2,4,6-TBP and PBP increased the level of reactive oxygen species (ROS), oxidized hemoglobin, and induced eryptosis [31][32][33]. Similarly, our previous research revealed that 2,4,6-TBP and PBP induced ROS formation, depleted ATP levels [34], and induced DNA strand breaks and DNA base oxidation in human peripheral blood mononuclear cells (PBMCs) [35]. It is known that ROS induction, the perturbation of energy production, and DNA damage are involved in apoptotic cell death [36].…”

A Review on Tetrabromobisphenol A: Human Biomonitoring, Toxicity, Detection and Treatment in the Environment

“…In human peripheral blood mononuclear cells, a lower concentration of TBBPA induced DNA damage, stimulated oxidative mutilation to pyrimidines and purines [ 104 ]. A low TBBPA concentration was known to down-regulate the transmembrane transport of the cell membrane-related genes and cellular skeleton, proving that the membrane damage was genetically controlled.…”

Endocrine disrupting chemicals in water and recent advances on their detection using electrochemical biosensors

“…18,19 However, adverse health effects on human beings need to be further investigated. Very recent studies on the carcinogenic nature of TCBPA and genotoxicity of TBBPA and TBBPS were elaborated by Lei et al 20 and Barańska et al, 21 respectively. TBBPA, TBBPS and TCBPA are known as common brominated flame retardants, and they are also often used in plastic paints, synthetic textiles, and electrical devices.…”