Differential sensitivity and responsiveness of three human cell lines HepG2, 1321N1 and HEK 293 to cadmium.
Cadmium (Cd) is a toxic heavy metal with no uniform mechanism of toxicity. In this the present study, the toxic effect of 5, 10 and 50 microM of Cd chloride was compared in three human cell lines; a human hepatoma cell line HepG2, a human astrocytoma cell line 1321N1, and a human embryonic kidney cell HEK 293. The results indicate a decrease in the viability of all three cell lines following exposure to Cd with HepG2 cells (IC50=13.96 microM) showing the most sensitivity when measured using the MTT assay. There was significant increase in lactate dehydrogenase leakage, DNA damage, malondialdeyde and antioxidant enzymes activities in all three cell lines especially at 50 microM Cd. Significant decreases in ATP production were also observed at all Cd concentrations in HepG2 and HEK 293 cell lines. ROS levels significantly increase and GSH/GSSG ratio significantly decrease in all the three cell lines after Cd exposure, but these effects were attenuated by the presence of N-acetylcysteine (NAC). The present study therefore shows that ROS production and glutathione (GSH) depletion may play a role in Cd-induced toxicity in all the three cell lines. The endogenous levels of protective enzymes as well as their responsiveness are likely to determine a cell's susceptibility to Cd.
Lawal
Akeem Olalekan
AO
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. akeem.lawal@strath.ac.uk
Ellis
Elizabeth
E
D000111:Acetylcysteine / Q000494:pharmacology; D019256:Cadmium Chloride / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D017382:Reactive Oxygen Species / Q000494:pharmacology
D017382:Reactive Oxygen Species; D005978:Glutathione; D019256:Cadmium Chloride; D000111:Acetylcysteine