Cell-cell proximity is a parameter affecting the transfer of mutagenic polycyclic aromatic hydrocarbons between cells

A keratinocyte cell-mediated mutation assay was used to examine the importance of cellular proximity to the transfer of mutagenic and cytotoxic polycyclic aromatic hydrocarbon (PAH) metabolites between cells. The PAHs 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP) were both mutagenic and cytotoxic to V-79 fibroblasts co-cultured on the surface of a keratinocyte feeder layer. However, neither PAH was mutagenic to the V-79 cells when the V-79 cells were co-incubated with the cultured keratinocytes under conditions in which the two cell types were separated by 0.5-1.5 mm but continually shared a common medium. Similarly, DMBA cytotoxicity was eliminated and BP-dependent cytotoxicity was greatly reduced in co-incubation protocols. These results suggest that cells must either be in contact or very close to facilitate the transfer of mutagenic PAH metabolites between cells.