Uptake and biological transformation of beta NiS and alpha Ni3S2 by human embryonic pulmonary epithelial cells (L132) in culture.
The cytotoxicity, biological transformation and interaction with plasma membranes of alpha Ni3S2 and beta NiS were studied on human embryonic pulmonary epithelial cells (L132 cell line) in culture. By establishing growth curves and survival curves, it was found that at equal molarity beta NiS has a higher inhibitory effect on cell growth than alpha Ni3S2 but a lower cytotoxic effect: the CL50 being 60 and 40 mumols/l respectively. As to their uptake, beta NiS crystals are preferentially phagocytized in their original form and then probably dissolved in the vacuoles, whereas alpha Ni3S2 is transformed in the extracellular space and in the phagocytic vacuoles into minute particles (10 nm) that are recovered bound to the cell membrane, phagocytic vacuoles and lysosomal membranes respectively. Energy dispersive spectrometry revealed that the particles bound to cell membranes no longer contain sulfur but only phosphorus and nickel as inorganic compounds. This observation suggests the formation of a Ni/P complex with the phosphate groups of membranous phospholipids and/or phosphotransferring proteins. The steady-state fluorescence polarization analysis, however, revealed a significant increase of membrane fluidity either induced by desaturation of aliphatic chains or directly by the cleavage of the fatty acid chains. These results clearly show a difference between beta NiS and alpha Ni3S2 concerning their cytotoxic effects, uptake, biological transformation and interaction with cell membranes.
Hildebrand
H F
HF
Institut de Médecine du Travail, INSERM Unité 124, Lille, France.
D'Hooghe
M C
MC
Shirali
P
P
Bailly
C
C
Kerckaert
J P
JP
D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D005333:Fetus; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008854:Microscopy, Electron; D009532:Nickel / Q000378:metabolism*; D013057:Spectrum Analysis
D002273:Carcinogens; D009532:Nickel; C017558:nickel sulfide; C017557:nickel subsulfide