Activation of the aryl hydrocarbon receptor (AhR)-mediated activity is one of key
events in toxicity of polycyclic aromatic hydrocarbons (PAHs). Although various classes
of AhR ligands may differentially activate human and rodent AhR, there is presently
a lack of data on the human AhR-inducing relative potencies (REPs) of PAHs. Here,
we focused on estimation of the AhR-mediated activities of a large set of environmental
PAHs in human gene reporter AZ-AhR cell line, with an aim to develop the human AhR-based
REP values with potential implications for risk assessment of PAHs. The previously
identified weakly active PAHs mostly failed to activate the AhR in human cells. The
order for REPs of individual PAHs in human cells largely corresponded with the available
data from rodent-based experimental systems; nevertheless, we identified differences
up to one order of magnitude in REP values of PAHs between human and rodent cells.
Higher REP values were found in human cells for some important environmental contaminants
or suspected carcinogens, such as indeno[1,2,3-cd]pyrene, benz[a]anthracene or benzo[b]fluoranthene,
while lower REP values were determined for methyl-substituted PAHs. Our results also
indicate that a different rate of metabolism for individual PAHs in human vs. rodent
cells may affect estimation of REP values in human cell-based assay, and potentially
alter toxicity of some compounds, such as benzofluoranthenes, in humans. We applied
the AZ-AhR assay to evaluation of the AhR-mediated activity of complex mixtures of
organic compounds associated with diesel exhaust particles, and we identified the
polar compounds present in these mixtures as being particularly highly active in human
cells, as compared with rodent cells. The present data suggest that differences may
exist between the AhR-mediated potencies of PAHs in human and rodent cells, and that
the AhR-mediated effects of polar PAH derivatives and metabolites in human cell models
deserve further attention.