BAY OR BAYLIKE REGIONS OF POLYCYCLIC AROMATIC-HYDROCARBONS WERE POTENT INHIBITORS OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION

Many polycyclic aromatic hydrocarbons (PAHs) are known carcinogens, an d a considerable amount of research has been devoted to predicting the tumor-initiating potential of PAHs based on chemical structure. Howev er, there has been little research into the effects of PAHs on the epi genetic events of tumor promotion and no structural correlation has be en made thereof. Gap junctional intercellular communication (GJIC) act ivity was used in this study as an epigenetic biomarker to determine t he structure-activity relationships of twelve different PAHs. The PAHs used were naphthalene, 1-methylnaphthalene, 2-methylnaphthalene, anth racene, 1-methylanthracene, 2-methylanthracene, 3-methylanthracene, 9, 10-dimethylanthracene, phenanthrene, fluorene, 1-methylfluorene, and f luoranthene. Results showed that PAHs containing bay or baylike region s inhibited GJIC more than did the linear PAHs. The nonnaphthalene PAH s were not cytotoxic as determined by a vital dye uptake assay, but th e naphthalene compounds were cytotoxic at the higher doses, indicating that the down regulation of GJIC by these naphthalenes could be a con sequence of general membrane damage. Inhibition of GJIC by all the inh ibitory PAHs was reversed when the cells were refreshed with PAH-free growth medium. Inhibition of GJIC occurred within 0.5-5 min and correl ated with the aqueous solubility of the PAHs. The present study reveal ed that there are structural determinants of epigenetic toxicity as de termined by GJIC activity.