Formation Mechanism and Toxicological Significance of Biogenic Mercury Selenide Nanoparticles in Human Hepatoma HepG2 Cells

Abstract

It is widely recognized that the toxicity of mercury (Hg) is attenuated by the simultaneous administration of selenium (Se) compounds in various organisms. In this study, we revealed the mechanisms underlying the antagonistic effect of sodium selenite (Na 2 SeO 3 ) on inorganic Hg (Hg 2+ ) toxicity in human hepatoma HepG2 cells. Observations by transmission electron microscopy indicated that HgSe (tiemannite) granules of up to 100 nm in diameter were accumulated in lysosomal-like structures in the cells. The HgSe granules were composed of a number of HgSe nanoparticles, each measuring less than 10 nm in diameter. No accumulation of HgSe nanoparticles in lysosomes was observed in the cells exposed to chemically synthesized HgSe nanoparticles. This suggests that intracellular HgSe nanoparticles were biologically generated from Na 2 SeO 3 and Hg 2+ ions transported into the cells and were not derived from HgSe nanoparticles formed in the extracellular fluid. Approximately 85% of biogenic HgSe remained in the cells at 72 h post culturing, indicating that biogenic HgSe was hardly excreted from the cells. Moreover, the cytotoxicity of Hg 2+ was ameliorated by the simultaneous exposure to Na 2 SeO 3 even before the formation of insoluble HgSe nanoparticles. Our data confirmed for the first time that HepG2 cells can circumvent the toxicity of Hg 2+ through the direct interaction of Hg 2+ with a reduced form of Se (selenide) to form HgSe nanoparticles via a Hg−Se soluble complex in the cells. Biogenic HgSe nanoparticles are considered the ultimate metabolite in the Hg detoxification process.

Ultracompact mirror device for forming 20-nm achromatic soft-X-ray focus toward multimodal and multicolor nanoanalyses

“…5a-c and the metal locations in Fig. 6a-c are consistent with previous studies that used conventional hard-X-ray fluorescence (XRF) microscopy [37][38][39][40] . This nanoscale method can only map the amount of high-Z elements; X-ray tomography 41 , phase contrast imaging 42 , and ptychography 43 are used to obtain missing information about cell morphology.…”

“…The second type of test specimen included air-dried biological cultures 37,59 for LEXRF microscopy. The specimens were cultured on inhouse Si wafer chips with 200-nm-thick silicon-nitride supporting film windows.…”

Ultracompact mirror device for forming 20-nm achromatic soft-X-ray focus toward multimodal and multicolor nanoanalyses

“…6a-c and the metal locations in Figs. 7a-c are consistent with previous studies that used conventional hard-X-ray fluorescence (XRF) microscopy [40][41][42][43]. This nanoscale method can only map the amount of high-Z elements; X-ray tomography [44], phase contrast imaging [45], and ptychography [46] are used to obtain missing information about cell morphology.…”

“…The second type of test specimen included air-dried biological cultures [40,58] for LEXRF microscopy. The specimens were cultured on in-house Si wafer chips with 200-nm-thick Si 3 N 4 supporting film windows.…”