cancer is a multistage multimechanism process involving gene and/or chromosomal mutations ( genotoxic events ) , altered gene expression at the transcriptional , translational , and post - translational levels ( epigenetic events ) , and altered cell survival ( proliferation and apoptosis or necrosis ) , resulting in an imbalance of the organism 's homeostasis . 
 maintenance of the organism 's homeostasis depends on the intricate coordination of genetic and metabolic events between cells via extracellular and intercellular communication mechanisms . 
 the release of a quiescent cell , whether normal or premalignant , from the suppressing effects of communicating neighbors requires the downregulation of intercellular communication via gap junctions , thereby allowing factors that control intracellular events to exceed a critical mass necessary for the cell to either proliferate or undergo apoptosis . 
 therefore , determining the role an environmental pollutant must play in the multistage carcinogenic process includes mechanisms of epigenetic toxicity such as the effects of a compound on gap junctional intercellular communication ( gjic ) . 
 a classic example of a class of compounds in which determination of carcinogenicity focused on genotoxic events and ignored epigenetic events is polycyclic aromatic hydrocarbons ( pahs ) . 
 the study of structure - activity relationships of pahs has focused exclusively on the genotoxic and tumor - initiating properties of the compound . 
 we report on the structure - activity relationships of two- to four - ringed pahs on gjic in a rat liver epithelial cell line . 
 pahs containing a bay or baylike region were more potent inhibitors of gjic than the linear pahs that do not contain these regions . 
 these are some of the first studies of determine the epigenetic toxicity of pahs at the epigenetic level.imagesfigure 1