Reversibility of Inhibition of Interferon-alpha/beta Induction by Benzo[a]pyrene2

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Abstract
Mouse L-929 cells were treated with benzo[a]pyrene [(BP) CAS: 50-32-8] for 24 hours. Several cultures of cells were immediately treated with polyriboinosinic-polyribocytidylic acid (poly I:C) to induce interferon-alpha/beta (IFN). Other sets of cultures were washed and allowed to incubate with fresh culture medium for 3–18 hours before addition of poly I:C to induce IFN. The IFN induction was severely inhibited in cells treated with BP and immediately challenged with poly I:C as compared to non-BP-treated cells. Up to a 6-hour delay in addition of poly I:C still resulted in severe inhibition of IFN induction; however, a delay of 9 hours or longer allowed the cells to recover their IFN production capacity. These data indicate that the inhibition of IFN induction by BP was reversible. The number of cells laid down in the cultures was approximately 6×105. In another experiment, the number of cells laid down in culture was serially decreased in several different cultures. These normal cells were then treated with poly I:C to induce IFN. A 50% decrease in the number of cells was required to reduce IFN production by 50%. In BP-treated L-929 cells, viabilities ranged from 88 to 90%, but IFN induction was inhibited by greater than 50%. These results suggest that toxicity of carcinogens to cells does not play a major role in inhibition of IFN induction by carcinogens.