Cell specific stress responses of cadmium-induced cytotoxicity

Cadmium is one of the age old toxic heavy metal, detrimental to the biological system. In this study, we explored the cellular and molecular mechanisms induced on exposure to different concentrations of cadmium chloride (CdCl2), on three different human cell lines with wild type p53, viz., A549, HEK293 and HCT116. We investigated whether the cellular responses followed, displayed any specific pattern related to their viability, mitochondrial respiration, DNA damage and apoptotic gene expression. All the cell lines showed decrease in viability following exposure to CdCl2. p53 was transcriptionally down regulated in all the three cell lines, but with different extents, in response to increasing concentration of cadmium. The cellular responses of the three cell lines were compared with that of a p53 knock out cell line (HCT116p53-/-). The p53 knock out cell line was highly sensitive to cadmium-induced toxicity; so was the cell line in which p53 mRNA expression was highly down regulated. This might implicate an unknown protective role of p53 signaling during heavy metal toxicity and that one of the possible mechanisms by which cadmium manifests its cytotoxic effect is through the transcriptional down regulation of p53 gene.