Effect of methamphetamine on clock genes and drug-metabolizing enzyme expression.

This study examined the association between clock gene expression and the effect of methamphetamine (MA) on drug-metabolizing enzymes from the perspective of drug metabolism. The relationship between expression of the clock genes and and the drug-metabolizing enzymes and was investigated using livers from autopsy cases of MA-intoxication deaths. Additionally, the effect of MA exposure on various genes was examined in HepG2 human hepatocellular carcinoma cells. Comparisons of the expression of various genes in MA users according to blood MA concentration revealed that expression was similar to that of , and expression was similar to that of . In cultured cell experiments, and expression decreased depending on the time elapsed after MA addition, and and expression increased slightly in a concentration-dependent manner. These results were consistent with the findings of autopsy examinations. Expression of and under and suppression, but not under suppression alone, was upregulated in response to MA. These results suggest that CYPs are regulated via the clock genes and during MA metabolism.