Abstract
Research and regulatory efforts in toxicology are increasingly focused on the development of suitable non-animal methodologies for human health risk assessment. In this work we used human intestinal Caco-2 and HT29/MTX cell lines to address the potential risks of mixtures of the emerging contaminants tetrabromobisphenol A (TBBPA) and commercial polystyrene nanoparticles (PSNPs). We employed different in vitro settings to evaluate basal cytotoxicity through three complementary endpoints (metabolic activity, plasmatic, and lysosomal membrane integrity) and the induction of the oxidative stress and DNA damage responses with specific endpoints. Although no clear pattern was observed, our findings highlight the predominant impact of TBBPA in the combined exposures under subcytotoxic conditions and a differential behavior of the Caco-2 and HT29/MTX co-culture system. Distinctive outcomes detected with the mixture treatments include reactive oxygen species (ROS) increases, disturbances of mitochondrial inner membrane potential, generation of alkali-sensitive sites in DNA, as well as significant changes in the expression levels of relevant DNA and oxidative stress related genes.
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