Does the Presence of Heavy Metals Influence the Gene Expression and Oxidative Stress in Bladder Cancer?

Heavy metal toxicity is associated with cancer progression. Studies have reported the relation between some metal ions and bladder cancer (BC). Direct influence of such agents in bladder carcinogenesis is still needed. Total 49 BC patients were included in the study. Level of Pb, Cr, Hg and Cd, oxidative stress markers, and gene expression of Bcl-2, Bax, IL-6, AKT, and P38 genes were detected in cancer and non-cancerous tissues obtained from bladder cancer patients. Concentrations of Pb, Cr, and Cd were significantly elevated in cancer tissues than normal, while Hg level was significantly increased in normal tissue than cancer. MDA level was significantly higher and SOD activity was lower in the cancer tissues compared to non-cancerous. The expressions of Bcl-2, IL-6, AKT, and P38 were significantly increased in the cancer tissues than in normal tissues while Bax level was significantly increased in non-cancerous tissue than in cancer tissue. In cancer tissue, there were significant correlations between Cr level with expression of Bax, AKT, and P38 while Cd level was significantly correlate with Bax, IL-6, AKT, and P38expression. The correlation between Cr and Cd with the expression of Bax, IL-6, AKT, and P38 may indicate a carcinogenic role of these metals on progression of bladder cancer.

Gene expression and oxidative stress markers profile associated with toxic metals in patients with renal cell carcinoma.

BACKGROUND: Toxic metals are associated with cancer progression. Studies have reported the relation between some toxic metals and renal cell carcinoma (RCC). METHODS AND RESULTS: Blood levels of Cd and Pb were determined in 94 RCC patients (RCC group) and 91 matched controls as well as blood level of malondialdehyde (MDA) and catalase (CAT) activity as markers of oxidative stress and antioxidant, respectively. Gene expression of MAP kinase pathway (P38 and JNK), hypoxia-inducible factor 1-alpha (HIF1α), vascular endothelial growth factor (VEGF), cytochrome C oxidase subunit 6 (COX6), metallothionein (MT2A), and heat shock protein (HSP90AA1) were evaluated in the obtained tissue specimens. Blood Cd and Pb levels were significantly higher in RCC group comparing to control group with preferential significant increase of Cd in chromophobe RCC (chRCC) sub-type. MDA level was significantly higher and CAT activity was lower in the RCC compared to controls. The difference was evident only in chRCC. The expressions of genes were significantly increased in the cancer tissues than in non-cancerous tissues in RCC sub-types and there was a significant correlation between Cd levels and expression of genes VEGF, MT2A, P38 and JNK in chRCC group. Immunohistochemical staining of clear cell RCC tissues shows a marked expression of VEGF and HIF-1α.While COX6 staining show marked expression in chRCC. CONCLUSIONS: There is a positive correlation between Cd toxicity and the development of RCC, especially chRCC sub-type. Cd is strongly incriminated in the pathogenesis of chRCC through the effort on some genes and oxidative stress markers.