Benzo[a]pyrene metabolites: effects on viral interferon induction

Benzo[a]pyrene (BaP) metabolites were assessed, with and without enzymatic activation by rat liver S9, for their inhibitory activities on influenza virus induction of interferon-alpha/beta (IFN-alpha/beta) in mammalian (LLC-MK2) cell cultures. Although BaP per se was inactive, metabolized BaP reduced viral IFN induction by approximately 80%. BaP metabolites (phenols, diols, 6-substituted derivatives) exhibited significant inhibitory activity (50% or greater) only when they were activated enzymatically. Although not significant, the diol metabolites without activation mildly reduced IFN induction on the average of 32%. The quinones did not adversely affect the IFN induction process, but three of the seven metabolites tested showed approximately 30% inhibitory activity in the presence of S9. BaP diol epoxides were direct inhibitors of viral IFN induction while derivatives of these epoxides, tetrols and triols, showed negligible inhibition even with S9. In general, the reported microbial mutagenicities of BaP metabolites could be correlated with their abilities to inhibit IFN induction. That activation-dependent hydrocarbons can be metabolized by S9 added to mammalian cell cultures resulting in the inhibition of viral IFN induction extends the capability and credibility for assessing suspect mutacarcinogens on this basis.