Epigenetic toxicity of a mixture of polycyclic aromatic hydrocarbons on gap junctional intercellular communication before and after biodegradation

Polycyclic aromatic hydrocarbons (PAHs) are known carcinogens, but most res earch on their toxicity in the development of human-risk assessment models has focused on genotoxicity. Many nongenotoxic PAHs, however, have been sho wn to be epigenetically toxic by disrupting gap junctional intercellular co mmunication (GJIC), an effect which has been affiliated with tumor promotio n. We therefore used GJIC as an epigenetic biomarker to assess the toxic ef fect of a nonaqueous phase liquid (NAPL) mixture of PAHs commonly found in coal tar and creosote products. The NAPL mixture consisted of toluene,napht halene, 1-methylnaphthalene, 2-ethylnaphthalene, acenaphthene, fluorene, ph enanthrene, fluoranthene, and pyrene. This mixture reversibly inhibited GJI C at a maximal and noncytotoxic dose of 60 mu M. Inhibition occurred within 5 min, indicating a post-translational modification of gap junction protei ns. Biodegradation of globules of this mixture suspended in mineral media b y a microorganism isolated from creosote-contaminated soils resulted in the removal of all but three heavy PAHs: acenaphthene, pyrene, and fluoranthen e. a reconstituted mixture of these three compounds showed results on GJIC activity identical to the original mixture relative to dose-, rate-, and ti me-responses, indicating that the toxicity of the PAHs was additive. The re sults suggest that bioremediation techniques that leave residual components of such NAPL mixtures in contaminated media can quantitatively but not qua litatively reduce their epigenetic toxic risk. Nonetheless, such bioresista nt residuals may be environmentally less mobile than the biodegraded compon ents of the precursor NAPLs.