Benzo(a)pyrene: kinetics of in vitro bioactivation in relation to inhibition of viral interferon induction.
J Interferon Cytokine Res 1988 Apr; 8(2):151-167
Studies were conducted to characterize benzo(a)pyrene (50328) (BaP) bioactivation kinetics in mammalian cell cultures in relation to the inhibition of viral interferon (IFN) induction and associated effects of BaP on the IFN system. Rhesus-monkey-kidney (LLC-MK2) and human-Chang-conjunctival (clone 1-5c-4) cell lines were used for induction and assay of IFN, respectively. IFN production in LLC-MK2 cell monolayers that were exposed for 20 hours to BaP with and without rat liver S9 and then to influenza virus inducer was monitored periodically for 48 hours. In cultures which were pretreated with BaP but without S9 activation the production of IFN occurred in a similar manner to that in the control cell cultures as regards rate, peak time, and magnitude of yield. In cultures with S9 activation the production rate was similar but the peak IFN level was reached 10 hours earlier and the yield was five fold less. A dose response relationship was demonstrated between the inhibition of viral IFN induction and concentrations of S9 as well as varying concentrations of BaP bioactivated by a constant S9 concentration. There was also a time dependency in the interaction of BaP, S9, and cells. Influenza virus replication attained a level 2.5 fold higher when cell cultures were pretreated with BaP plus S9 rather than either BaP or S9 alone. IFN levels were four times higher when cells were treated with either BaP or S9 than when the combination was used. Metabolized BaP not only hindered IFN induction but also slowed the production phase of IFN. BaP did not interfere with the ability of IFN to confer antiviral cellular resistance. As the impairment of IFN induction by BaP is reversible, periodic or continual cellular exposure to BaP is required if the IFN induction is to be sustained.
NIOSH-Author; Polycyclic-aromatic-hydrocarbons; Carcinogens; Cell-biology; Viral-infections; Metabolic-study; Protein-chemistry; In-vitro-studies; Mammalian-cells
Journal of Interferon and Cytokine Research