Inhibition of intercellular communication in human keratinocytes by fractionated asphalt fume condensates.
Asphalt fume condensate (AFC) and chromatographically separated fractions have been shown to cause cancer in mouse skin. The levels of known carcinogenic initiators in these complex mixtures, however, are considered too low to account for their carcinogenic potency. It has been proposed that AFC may contain co-carcinogenic or tumor-promoting agents in addition to carcinogenic initiators. Modulation of gap junctional intercellular communication (GJIC) has been implicated as an important effect of tumor promoters. In this study, we examined the effect of five chromatographically generated fractions of AFC on GJIC in cultured human epidermal keratinocytes (HEK). HEK cells were exposed overnight to medium containing DMSO extracts of AFC fractions. GJIC was evaluated by dye-coupling of microinjected Lucifer Yellow CH. All AFC fractions produced a concentration-dependent inhibition of GJIC. The apparent potency of each fraction correlated with its relative polarity based on HPLC elution characteristics. Cells with reduced GJIC as a result of AFC fraction exposure were found to exclude propidium iodide, suggesting that inhibition of GJIC occurred in the absence of cell killing. However, significantly reduced culture DNA content was found following the overnight exposure to the highest concentrations of AFC fractions C, D and E.
Wey
H E
HE
Centers for Disease Control, National Institute for Occupational Safety and Health, Division of Biomedical and Behavioral Science, Cincinnati, OH 45226.
Breitenstein
M J
MJ
Toraason
M A
MA
D002450:Cell Communication / Q000187:drug effects*; D016923:Cell Death; D006801:Humans; D006838:Hydrocarbons / Q000737:chemistry / Q000633:toxicity*; D007365:Intercellular Junctions / Q000187:drug effects*; D015603:Keratinocytes / Q000187:drug effects*
D006838:Hydrocarbons; C006647:asphalt