LOCAL-MEDIATED AND SYSTEMIC-MEDIATED SUPPRESSION OF CONTACT HYPERSENSITIVITY IN MICE BY SEVERAL STRUCTURALLY UNRELATED CLASSES OF TUMOR PROMOTERS

Several structurally unrelated classes of chemicals defined as promoters in the murine skin multistage carcinogenesis protocol were surveyed for their abilities to modify contact hypersensitivity (CHS) responses in SENCAR mice. Sensitization of dorsal skin with 2,4-dinitrofluorobenzene (DNFB) and subsequent challenge of ears 5 days later with DNFB resulted within 24 h in ear swelling. Pretreatment of dorsal skin with multiple applications (2 X/week for 2 weeks) of promoting doses of 12-O-tetradecanoylphorbol-13-acetate (TPA), anthralin, butylated hydroxytoluene hydroperoxide, n-dodecane and ethyl phenylpropiolate (EPP) prior to sensitization with DNFB inhibited, to a comparable extent, the subsequent induction of CHS by DNFB challenge. Pretreatment of dorsal skin with promoting doses of benzoyl peroxide resulted in reproducible, but diminished suppression of CHS, relative to that mediated by the other chemical promoters. Application of promoting doses of TPA, anthralin and EPP, but not the other chemicals, to ventral skin prior to DNFB sensitization of dorsal skin also significantly inhibited DNFB-induced CHS. However, suppression of CHS mediated by ventral application of these three chemicals was quantitatively less than that occurring when the chemicals were applied to the site of DNFB sensitization. Collectively, these studies demonstrate that various classes of structurally unrelated tumor promoters have in common the ability to suppress CHS, a cell-mediated immune response. Furthermore, some tumor promoters exert their suppressive effects through both local and systemic processes.