Cigarette smoke condensate and individual constituents modulate DNA methyltransferase expression in XXXX liver cells.

@entity1 @entity137 @entity1239 @entity4874 @entity15894
OBJECTIVES: Previous studies found higher expression levels of DNA methyltransferase 1 in liver samples from smokers compared to those from non-smokers. In contrast, expression levels of DNA methyltransferase 3a and @entity15894 were similar in smokers and non-smokers. This study extends these studies to establish a causal linkage to cigarette smoke exposure by examining whether DNA methyltransferase expression is modulated by cigarette smoke condensate. METHODS: These experiments were conducted in an in vitro system using HepG2 @entity1 liver cells. The dose range of cigarette smoke condensate was 0.1-120     g/mL. The duration of exposure was up to 72   h. RESULTS: In a 24-h exposure, DNA methyltransferase 1 expression was found to increase significantly in a dose-dependent manner (greater than threefold at 100     g/mL cigarette smoke condensate). Expression levels of DNA methyltransferase 3a and @entity15894 were, however, not affected under these conditions. The effect of two cigarette constituents, @entity1239 and @entity4874 , on DNA methyltransferase 1 expression was also examined. @entity1239 exposure significantly increased DNA methyltransferase 1 expression in a dose-dependent manner (greater than twofold at 50     M). However, under these conditions, @entity4874 did not increase DNA methyltransferase 1 expression. CONCLUSION: These results clearly provide additional support of the modulating effect of cigarette smoke on DNA methyltransferase 1 expression. Given the potential of alterations in DNA methyltransferase expression to affect cellular function, this pathway may play a critical role in cigarette smoke-induced @entity137 .
