Cell specific stress responses of cadmium-induced cytotoxicity

Abstract

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 (CdCl 2 ), 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 CdCl 2 . 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. ARTICLE HISTORY

2D-Coordination polymers based on 1H-indazole-4-carboxylic acid and transition metal ions: magnetic, luminescence and biological properties

“…In fact, previous studies demonstrated that Cd exhibits dosedependent toxicity on different cell lines. 30 However, these preliminary in vitro results should be complemented with further experiments to further evaluate the observed cell-type specificity.…”

The role of autophagy in cadmium-induced acute toxicity in glomerular mesangial cells and tracking polyubiquitination of cytoplasmic p53 as a biomarker

“…Thus, prostate cancer cells with insufficient p53 expression or those expressing mutant p53 are resistant to Cd-induced apoptosis 29 . In contrast, a protective role of p53 against Cd-induced cytotoxicity has been reported in A549, HEK293, and HCT116 cells 30 . In that study, Cd exposure downregulated p53 at the transcriptional level in wild-type HCT116 (p53 +/+ ) cells.…”

Transforming early pharmaceutical assessment of genotoxicity: applying statistical learning to a high throughput, multi end point in vitro micronucleus assay

“…In the development of this assay, all test compounds were solubilised in DMSO, although the solubility of cadmium chloride in DMSO (1800 g/l (25 °C) is similar to in water [1400 g/l (25 °C)], it is possible that the acoustic dosing technologies utilised in this assay may not be compatible with dosing metal salt solutions. In multiple cell lines, Cadmium induced DNA damage is observed at relatively high doses that are associated with cytotoxicity (500, 1000 and 2000 µM) 44 furthermore A549 cells have been shown to exhibit tolerance towards cadmium induced cell death when compared to other lines (HEK293, HC116p53wt and HC116p53 −/− and CHO-9) 45 , 46 , highlighting the potential cell line and dose specific effects of this compound that may contribute to the lack of response observed in this assay. To assess this prolonged treatment regimens, with and without the inclusion of a recovery period, as well as a broader dose range could be assessed.…”