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.