Epigenetics, an early event in the modulation of gene expression by inositol hexaphosphate in ethylnitrosourea exposed mouse lungs

Nutr Cancer. 2011;63(1):89-99. doi: 10.1080/01635581.2010.516868.

Abstract

Mechanisms of anticancer effects of inositol hexaphosphate are not fully understood. Epigenetic changes are the early changes in tumorigenesis. DNA methyl transferases, methyl CpG binding proteins, methyl CpG DNA binding domain protein, and histone deacetylases are the major molecules involved in epigenetics. We have shown the effects of IP6 at the molecular level in mouse lungs before the tumor is developed. After 3 mo of ENU exposure, there was no tumor formation, but there was hyperplasia and lymphocytic infiltration in the lungs. Inflammation and DNA damage repair enzymes COX-2 and MLH1 appear to be upregulated, whereas tumor suppressor gene p16 was downregulated by ENU. On the other hand, ENU exposure more or less upregulated the epigenetic events such as the expressions of DNMT1, MeCP2, MBD1, and HDAC1. This alteration was reduced by IP6 administration. Results were supported by modulation of global DNA methylation and the modulation of promoter CpG methylation of p16, MLH1, and COX-2 genes. Hence, this study indicates the possible role of epigenetics at the early stage of tumor development and in the regulation of gene expression by IP6 before the onset of ENU-induced lung tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methylation
  • Epigenesis, Genetic*
  • Ethylnitrosourea / toxicity*
  • Female
  • Gene Expression Regulation / drug effects*
  • Histone Deacetylase 1 / genetics
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Methyl-CpG-Binding Protein 2 / genetics
  • Mice
  • Phytic Acid / pharmacology*

Substances

  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Phytic Acid
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human
  • Dnmt1 protein, mouse
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Ethylnitrosourea