Pro-oxidative toxicity of cells in suspension does not point to a cell cultural artefact as an explanation of the increased susceptibility of alveolar epithelial-like cells after glucocorticoid pretreatment.

The influence of cell numbers on peroxide-(tertiary butylhydroperoxide (tBHP) or hydrogen peroxide-(HP)) or zinc-(zinc chloride) induced oxidative stress was assessed in alveolar epithelial-like cell lines in this work. Differences in cell numbers change the cellular glutathione and glutathione reductase activity as well as the amount of exported glutathione and therefore might influence susceptibility against oxidative stress. Toxicity due to zinc decreased, toxicity due to HP increased, while tBHP-mediated toxicity was unchanged in our experiments when cells were exposed in suspension as compared to monolayers.

Enhancing glutathione synthesis can decrease zinc-mediated toxicity.

Zinc toxicity has been linked to cellular glutathione: A decrease in glutathione is followed by an increase in zinc-mediated toxicity. The question arises whether an increase in glutathione synthesis might decrease zinc-mediated cytotoxicity. We incubated five cell lines (hepatoma and lung-derived) with zinc chloride and 2 mmol/l N-acetyl-L-cysteine (NAC) to support glutathione synthesis.