Diethanolamine Alters Proliferation and Choline Metabolism in Mouse Neural Precursor Cells

Abstract

Diethanolamine (DEA) is a widely used ingredient in many consumer products and in a number of industrial applications. It has been previously reported that dermal administration of DEA to mice diminished hepatic stores of choline and altered brain development in the fetus. The aim of this study was to use mouse neural precursor cells in vitro to assess the mechanism underlying the effects of DEA. Cells exposed to DEA treatment (3mM) proliferated less (by 5-bromo-2-deoxyuridine incorporation) at 48 h (24% of control [CT]), and had increased apoptosis at 72 h (308% of CT). Uptake of choline into cells was reduced by DEA treatment (to 52% of CT), resulting in diminished intracellular concentrations of choline and phosphocholine (55 and 12% of CT, respectively). When choline concentration in the growth medium was increased threefold (to 210 microM), the effects of DEA exposure on cell proliferation and apoptosis were prevented, however, intracellular phosphocholine concentrations remained low. In choline kinase assays, we observed that DEA can be phosphorylated to phospho-DEA at the expense of choline. Thus, the effects of DEA are likely mediated by inhibition of choline transport into neural precursor cells and by altered metabolism of choline. Our study suggests that prenatal exposure to DEA may have a detrimental effect on brain development.

Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

“…As far as we know, the cytotoxicity of diethanolamine have not been well investigated, and most of previous studies have limited to non-human creatures such as aquatic biota [35] . Treatment of cultured mouse neural precursor cells with diethanolamine reduced the intracellular uptake and accumulation of choline [36] . When pregnant mice were treated dermally with diethanolamine, apoptosis was induced in the hippocampal ventricular zone of the brain of fetuses [37] .…”

ToxCast chemical library screen identifies diethanolamine as an activator of Wnt signaling

“…Our data suggests that genetic background (i.e. UBE3A T485A expression) greatly enhances the effects of DEA on Wnt signaling (Figure 5b), and that DEA increases human NPC proliferation at relatively low concentrations (Figure 5c,d)(70). Given these findings, the predicted high level of exposure in humans, including women of childbearing age, additional studies are warranted, particularly with regard to exposure and neurodevelopmental outcomes in genetically sensitized backgrounds.…”

“…DEA is structurally similar to endogenous ethanolamine and choline. Cells and animals treated with DEA phenocopy choline deficiency, likely via competitive inhibition of choline metabolism(70, 73). However, there are no previous reports linking DEA to Wnt signaling, nor to any other developmental signaling pathways.…”

“…Notably, DEA activated the Wnt reporter at 100-fold lower concentrations when transfected with UBE3A T485A (Figure 5b). DEA has previously been shown to decrease proliferation and increase apoptosis of mouse NPCs in vitro and in vivo (70, 71). In vivo , DEA affects hippocampal NPC proliferation at 80 mg/kg(71), which is substantially higher than what is predicted for human exposure (~0.0038 mg/kg bodyweight per day).…”

Safety Assessment of Diethanolamine and Its Salts as Used in Cosmetics

“…In a study to identify the potential mechanism for the alterations described above, mouse neural precursor cells were treated in vitro with diethanolamine. 51 Cells exposed to 3 mM diethanolamine had less cell proliferation at 48 hours and had increased apoptosis at 72 hours. Diethanolamine treatment decreased choline uptake into the cells, resulting in diminished choline and phosphocholine.…”