Tumor-promoting activity of 2,4-dinitrofluorobenzene

The aim of this study was to determine whether the skin-sensitizing agent 2,4-dinitrofluorobenzene (DNFB) would elicit the same morphological and biochemical events that are characteristic of 12-O-tetradecanoylphorbol-13-acetate (TPA). While single applications of 0.1% or 0.2% DNFB produced only mild epidermal hyperplasia, multiple applications produced pronounced hyperplasia. Compared with TPA, a single application of DNFB produced small increases in ODC activity, although a second DNFB treatment produced a greater response. Both DNFB and TPA caused marked induction of ODC, c-fos and c-jun mRNA. Vascular permeability increased significantly in response to DNFB, such that after 15 hr the response was quantitatively the same as for TPA. Repeated TPA produced the same response as a single application, but repeated DNFB resulted in a response that was half that of TPA. In contrast to TPA, DNFB failed to activate partially purified protein kinase C (PKC), although it did cause transient down-regulation of activity 15 hr after treatment. The ability of DNFB to induce ODC activity, however, was unaffected by prior down-regulation of PKC. DNFB was also shown to promote tumors in initiated SSIN mice. Twice-weekly applications of 0.1% or 0.2% DNFB resulted in approximately 65% and 85% of the mice developing an average of 2.0 or 3.2 tumors each, respectively. These results demonstrate that DNFB elicits many of the same changes as TPA and that it does so in a PKC-independent manner.