The effect of copper on the mRNA expression profile of xenobiotic-metabolizing enzymes in cultured rat H4-II-E cells.

Copper (Cu(2+)) is an essential element that plays important roles in physiological functions of the body. However, high Cu(2+) levels can have toxic implications. This study aims to investigate the constitutive response to Cu(2+) exposure of xenobiotic-metabolizing enzymes in cultured rat liver (H4-II-E) cell lines. Rat cells were exposed to copper sulfate (0-500 μM) for 24 h. The effects of Cu(2+) on the messenger RNA (mRNA) expressions of phase I and II enzymes and regulatory elements were examined using real-time PCR. Metallothionein mRNA expression was induced in a dose-dependent manner after treatment with Cu(2+). mRNA expressions of phase I enzymes such as cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2) were slightly induced after exposure to low concentrations of Cu(2+); however, CYP1A1 and CYP1A2 mRNA expressions were significantly downregulated at higher Cu(2+) concentrations. These effects corresponded with expression of aryl hydrocarbon receptor mRNA. The mRNA expressions of phase II enzymes were reduced upon exposure to Cu(2+). In conclusion, phase I and II enzyme expressions were significantly modulated upon Cu(2+) exposure. These results indicated that Cu(2+) exposure had toxicological implications for cultured H4-II-E cells.