title: Cigarette smoke condensate and individual constituents modulate DNA methyltransferase expression in human liver cells.
abstract: OBJECTIVE
  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 DNA methyltransferase 3b 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 human liver cells. The dose range of cigarette smoke condensate was 0.1-120 µg/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 µg/mL cigarette smoke condensate). Expression levels of DNA methyltransferase 3a and DNA methyltransferase 3b were, however, not affected under these conditions. The effect of two cigarette constituents, nicotine and cotinine, on DNA methyltransferase 1 expression was also examined. Nicotine exposure significantly increased DNA methyltransferase 1 expression in a dose-dependent manner (greater than twofold at 50 µM). However, under these conditions, cotinine did not increase DNA methyltransferase 1 expression.
  
  
  CONCLUSIONS
  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 toxicity.
authors.affiliation: National Center for Toxicological Research, Jefferson, AR, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: National Center for Toxicological Research, Jefferson, AR, USA.
authors.forename: Beverly
authors.initials: B
authors.lastname: Word
authors.affiliation: National Center for Toxicological Research, Jefferson, AR, USA.
authors.forename: Lascelles
authors.initials: L
authors.lastname: Lyn-Cook
authors.affiliation: National Center for Toxicological Research, Jefferson, AR, USA.
authors.forename: Beverly
authors.initials: B
authors.lastname: Lyn-Cook
authors.affiliation: National Center for Toxicological Research, Jefferson, AR, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hammons
keywords: Cigarette smoke condensate; DNA methyltransferase; human liver cells; nicotine