Increased cytotoxicity of carbon tetrachloride in a human hepatoma cell line overexpressing cytochrome P450 2E1.
Cytotoxic free radicals generated during the metabolism of carbon tetrachloride by cytochrome P450 2E1 (CYP2E1) are thought to cause hepatotoxicity. Here, the cytotoxic effects of carbon tetrachloride in a liver cell line expressing CYP2E1 (HLE/2E1) are compared with those in the mother cell line (HLE). The effects of carbon tetrachloride on the gene expression of HSP70, a potential marker of oxidative stress, were also examined. The viability of HLE/2E1 cells after exposure to carbon tetrachloride was significantly decreased compared with that of HLE cells. Northern blot analysis revealed that the HSP70 mRNA level was significantly increased after carbon tetrachloride treatment in both cell lines, while the magnitude of its increase was much greater in HLE/2E1 cells than in HLE cells. These results suggest that the oxidative stress induced by CYP2E1 plays an important role in the increase in cytotoxicity of carbon tetrachloride in CYP2E1-overexpressing cells.
Takahashi
S
S
Department of Anaesthesiology and Resuscitology, Okayama University Medical School, Okayama City, Japan.
Takahashi
T
T
Mizobuchi
S
S
Matsumi
M
M
Morita
K
K
Miyazaki
M
M
Namba
M
M
Akagi
R
R
Hirakawa
M
M
D015152:Blotting, Northern; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002461:Cell Line, Transformed; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1