Organophosphorus Flame Retardant TDCPP Displays Genotoxic and Carcinogenic Risks in Human Liver Cells

Tris(1,3-Dichloro-2-propyl)phosphate (TDCPP) is an organophosphorus flame retardant (OPFR) widely used in a variety of consumer products (plastics, furniture, paints, foams, and electronics). Scientific evidence has affirmed the toxicological effects of TDCPP in in vitro and in vivo test models; however, its genotoxicity and carcinogenic effects in human cells are still obscure. Herein, we present genotoxic and carcinogenic properties of TDCPP in human liver cells (HepG2). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and neutral red uptake (NRU) assays demonstrated survival reduction in HepG2 cells after 3 days of exposure at higher concentrations (100–400 μM) of TDCPP. Comet assay and flow cytometric cell cycle experiments showed DNA damage and apoptosis in HepG2 cells after 3 days of TDCPP exposure. TDCPP treatment incremented the intracellular reactive oxygen species (ROS), nitric oxide (NO), Ca2+ influx, and esterase level in exposed cells. HepG2 mitochondrial membrane potential (ΔΨm) significantly declined and cytoplasmic localization of P53, caspase 3, and caspase 9 increased after TDCPP exposure. qPCR array quantification of the human cancer pathway revealed the upregulation of 11 genes and downregulation of two genes in TDCPP-exposed HepG2 cells. Overall, this is the first study to explicitly validate the fact that TDCPP bears the genotoxic, hepatotoxic, and carcinogenic potential, which may jeopardize human health.

Structural property and risk assessment of loose deposits in drinking water distribution systems

Discoloration events caused by loose deposits resuspension in drinking water distribution systems (DWDS) are main aspects of customer complaints across the world, but the understanding of the potential risks of loose deposits is insufficient. In this study, loose deposits in real DWDS were collected from regions frequently experiencing ‘yellow water’. Cytotoxicity of healthy human liver cells was used to evaluate the toxicity risks of the particle samples. The results showed that the loose deposits would have a realistic discoloration risk (turbidity > 10 NTU) when their concentrations were higher than 10 mg/L. The water sample containing 1,000 mg/L loose deposits had dark yellow color (100–300 PCU) and cytotoxicity (viability of human liver cells during cytotoxicity tests 59.18–80.69%), while the water sample containing 1 mg/L loose deposits did not have obvious color (<15 PCU) and cytotoxicity (>97.00%). Particle size showed a stronger correlation with relative viability (r = 0.761) than other properties (specific area, metal content, contact angle, saturation magnetization and electron transfer number). However, it is interesting to notice that both turbidity and color had a low correlation with relative viability, thus the toxicity of the particles could not be properly judged using turbidity or color. This study gives an important guidance that though the loose deposits could be visualized during water discoloration, its toxicity risks could not be evaluated through aesthetic indicators.

Progesterone-Mediated Enhancement of Hepatitis E Virus Replication in Human Liver Cells

Hepatitis E is usually a self-limiting acute disease; however, during pregnancy, a severe form of fulminant hepatic failure and high mortality rate are associated with hepatitis E virus (HEV) infection. Increased levels of progesterone and HEV RNA are observed in pregnant women with fulminant hepatic failures.

Bioengineered Liver Models for Investigating Disease Pathogenesis and Regenerative Medicine

Owing to species-specific differences in liver pathways, in vitro human liver models are utilized for elucidating mechanisms underlying disease pathogenesis, drug development, and regenerative medicine. To mitigate limitations with de-differentiated cultures, bioengineers have developed advanced techniques/platforms, including micropatterned cocultures, spheroids/organoids, bioprinting, and microfluidic devices, for perfusing cell cultures and liver slices. Such techniques improve mature functions and culture lifetime of primary and stem-cell human liver cells. Furthermore, bioengineered liver models display several features of liver diseases including infections with pathogens (e.g., malaria, hepatitis C/B viruses, Zika, dengue, yellow fever), alcoholic/nonalcoholic fatty liver disease, and cancer. Here, we discuss features of bioengineered human liver models, their uses for modeling aforementioned diseases, and how such models are being augmented/adapted for fabricating implantable human liver tissues for clinical therapy. Ultimately, continued advances in bioengineered human liver models have the potential to aid the development of novel, safe, and efficacious therapies for liver disease.