Zinc has ambiguous effects on chromium (VI)-induced oxidative stress and apoptosis.

Zinc is an important cellular antioxidant. We investigated its role in chromium-induced oxidative stress and apoptosis in human tumor cell line Hep-2. The measured parameters included intracellular labile zinc content (Zinquin-E fluorescence), cell viability (WST-1 assay), oxidative stress (spectrophotometry), mitochondrial potential (flow cytometry), caspase-3 activity, and PARP cleavage (immunofluorescence). We found that Hep-2 cells contain abundant labile zinc stores that may be depleted by the ionophore TPEN or increased by external zinc supplementation. Chromium (VI)-induced cytotoxicity and apoptosis were enhanced in zinc-depleted cells after 24 h, in particular at chromium (VI) concentrations of 50 and 150 micromol/l. On the other hand, elevated levels of labile zinc were able to protect against apoptosis induced by 10 micromol/l chromium (VI) but at higher chromium (VI) concentrations (50 and 150 micromol/l) acted synergistically, significantly enhancing oxidative stress and the course of apoptosis, possibly through oxidative stress and mitochondrial damage.