Long and short fiber amosite asbestos alters at a different extent the redox metabolism in human lung epithelial cells.
The mechanism by which asbestos fibers are fibrogenic and tumorigenic is still matter of debate. The higher pathogenicity of longer fibers has been traditionally associated with their slower clearance in respiratory airways. However, short amosite fibers, obtained by grinding longer ones, exhibited a lower potential to damage nude DNA and a lower in vitro cytotoxicity. We have thus revisited the two sets of long and short fibers in order to compare their surface properties to their activity in cell systems. In this study we report that, in human lung epithelial cells A549, long amosite fibers, more effectively than the short ones, initiate free radical reactions, inhibit the glucose 6-phosphate dehydrogenase activity and the pentose phosphate pathway, decrease the intracellular level of reduced glutathione, and increase the generation of thiobarbituric acid reactive substances and the leakage of lactate dehydrogenase in the extracellular medium. These results suggest that the shortening of fibers by prolonged milling affects not only their biopersistence, but also their surface properties, hence their interaction with cellular metabolism. Our data provide also a mechanism by which asbestos fibers inhibit the pentose phosphate pathway, i.e., via the oxidative inhibition of glucose 6-phosphate dehydrogenase, which is prevented by reduced glutathione.
Riganti
Chiara
C
Interdepartmental Center G. Scansetti for Studies on Asbestos and other Toxic Particulates, University of Torino, Torino, Italy.
Aldieri
Elisabetta
E
Bergandi
Loredana
L
Tomatis
Maura
M
Fenoglio
Ivana
I
Costamagna
Costanzo
C
Fubini
Bice
B
Bosia
Amalia
A
Ghigo
Dario
D
D000818:Animals; D017639:Asbestos, Amosite / Q000633:toxicity*; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D004578:Electron Spin Resonance Spectroscopy; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019016:Mineral Fibers / Q000633:toxicity*; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013499:Surface Properties; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D002273:Carcinogens; D005609:Free Radicals; D019016:Mineral Fibers; D017392:Thiobarbituric Acid Reactive Substances; D017639:Asbestos, Amosite; D012313:RNA; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione