Different cellular responses evoked by natural and stoichiometric synthetic chrysotile asbestos.
The carcinogenic potency of asbestos, including chrysotile, is well established. Several physico-chemical features of the fibers appear implied, such as fibrous habit, size, crystallinity, morphology, and surface active metal ions, where free radical generation may take place. In contrast to other asbestos forms, iron is not a stoichiometric component of chrysotile, but is only present together with other extraneous ions as a magnesium- and silicon-replacing contaminant. To determine the role played by contaminating ions and morphological features of the fibers, a stoichiometric chrysotile with constant structure and morphology was synthesized in hydrothermal conditions. Free radical generation and the effects of these fibers on human lung epithelial A549 cells have been compared to that elicited by a well known toxic natural chrysotile (UICC A, from Rhodesia). After a 24-h incubation, the natural, but not the synthetic, form exerted a cytotoxic effect, detected as leakage of lactate dehydrogenase. Homolytic rupture of a C-H bond and lipoperoxidation in A549 cells took place in the presence of the natural, but not of the synthetic, chrysotile. Antioxidant systems were also affected differently. The pentose phosphate pathway and its regulatory enzyme glucose 6-phosphate dehydrogenase were markedly inhibited only by the natural specimen, which also caused a depletion of intracellular reduced glutathione in A549 cells. These results suggest that metal ions, fiber size and state of the surface play a crucial role in the oxidative stress caused by chrysotile asbestos. Stoichiometric synthetic fibers may thus be proposed as a reference standard (negative control) for toxicological studies.
Gazzano
Elena
E
Dipartimento di Genetica, Biologia e Biochimica-Sezione di Biochimica, Università di Torino, Via Santena 5/bis-10126 Torino, Italy.
Foresti
Elisabetta
E
Lesci
Isidoro Giorgio
IG
Tomatis
Maura
M
Riganti
Chiara
C
Fubini
Bice
B
Roveri
Norberto
N
Ghigo
Dario
D
D000975:Antioxidants / Q000378:metabolism; D017632:Asbestos, Serpentine / Q000737:chemistry* / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System / Q000378:metabolism; D003460:Crystallization; D004785:Environmental Pollutants / Q000633:toxicity*; D005609:Free Radicals / Q000819:agonists; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D020545:Respiratory Mucosa / Q000166:cytology; D013054:Spectrophotometry, Atomic
D000975:Antioxidants; D017632:Asbestos, Serpentine; D004785:Environmental Pollutants; D005609:Free Radicals