Differential sensitivity and responsiveness of three human cell lines HepG2, 1321N1 and HEK 293 to cadmium

Abstract

-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 μM 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 (IC 50 = 13.96 μM) 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 μM 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.

Cadmium Impairs p53 Activity in HepG2 Cells

“…Cadmium induces DNA damage in HepG2 cells, as previously reported [22, 23], and as confirmed by our experiments on single-strand breaks formation (data not shown).…”

“…(1) Cadmium is accumulated into HepG2 cells [21] and indirectly causes a genotoxic damage [22, 23] (data not shown); (2) the p53 is visualized into the nucleus, as expected, to exert its function of transcription factor; (3) the p21 Cip1/WAF-1 gene ( p21 mRNA) is upregulated, although no protein upregulation is observed possibly due to a posttranscriptional regulation by miRNA-372; (4) no cell cycle arrest is observed, thus leading to the transmission of DNA damage and ultimately to cancer.…”

Lanthionine Synthetase C-like Protein 1 Interacts with and Inhibits Cystathionine β-Synthase

“…The basal GSH/GSSG ratio in transfected HEK293 cells was 13.8 Ϯ 1.1 (mean Ϯ S.E. ), which is not significantly different from previous reports (25,26). Compared with control, treatment with 100 M H 2 O 2 for 2 h significantly lowered the GSH/GSSG ratio to 6.9 Ϯ 0.7 but did not affect the total glutathione (GSHϩGSSG) level (Fig.…”

Connexin43 Hemichannels Contribute to Cadmium-Induced Oxidative Stress and Cell Injury

“…As for molecules responsible for the hemichannel-mediated effects on oxidative stress, GSH could be the likely candidate. GSH has been documented to be depleted in Cd 2 + -treated cells (23). As a major oxygen radical scavenger, GSH provides the first line of defense against Cd 2 + -elicited oxidative stress and cell injury (20).…”

“…Most of the toxic effects of Cd 2 + are mediated by oxidative stress (26,52). Cd 2 + promotes the formation of oxygen free radicals (12) and decreases the concentration of the important antioxidant glutathione (GSH) (23,29). Modulation of intracellular redox status or inhibition of the stress-related signal such as c-Jun N-terminal kinase ( JNK) has been documented to attenuate and even prevent Cd 2 + -initiated cell injury (37,40,52).…”