METABOLIC REQUIREMENTS FOR INDUCTION OF CONTACT HYPERSENSITIVITY TO IMMUNOTOXIC POLYAROMATIC HYDROCARBONS

Experiments were performed to define the metabolic requirements for in duction of contact hypersensitivity to polyaromatic hydrocarbons (PAHs ), environmental xenobiotics that are both immunotoxic and carcinogeni c. Evidence that conversion of the parent compound to a reactive metab olite was necessary for the development of contact hypersensitivity in cluded the fact 1) that contact hypersensitivity to the polyaromatic h ydrocarbon dimethylbenz(a)anthracene (DMBA) only occurred in strains o f mice that could metabolize the compound, 2) that among the PAHs, onl y those that could induce aryl hydrocarbon hydroxylase, the rate-limit ing enzyme in the PAH metabolic pathway, were immunogenic, and 3) that inhibitors of PAH metabolism reduced DMBA contact hypersensitivity. C ells from the XS52 Langerhans cell-like dendritic cell line were able to metabolize the PAH benzo(a)pyrene to its diol, quinone, and phenol metabolites, GM-CSF augmented benzo(a)pyrene metabolism in XS52 cells. Finally, in vivo depletion of CD8(+), but not CD4(+), T cell populati ons inhibited contact hypersensitivity to DMBA. The implications of th ese experiments are that at least for some contact allergens, the meta bolic status of the host is a key determinant of individual susceptibi lity to the development of allergic contact dermatitis, and the metabo lic pathway of an individual hapten may have ramifications for the T c ell subpopulation-CD4 or CD8-that is activated.