The effect of the
corticosteroid fluocinolone acetonide (FA) on skin
tumor induction and
inflammation by the contact sensitizer
dinitrofluorobenzene (
DNFB) was examined. This study broadly relates to the question of whether contact sensitizers, as electrophilic chemicals that produce
protein adduction, may constitute an environmental
cancer hazard. The specific aim of this study was to evaluate the extent to which the immunogenic inflammatory response to
DNFB, in contrast to
DNFB cytotoxicity, might be responsible for
tumor induction. Experiments were conducted on a transgenic (TG.AC) mouse, incorporating a mutated ras oncogene (v-Ha-ras) that responds rapidly and profusely with skin
papillomas to
tumor promoters as if it were genetically initiated. Various doses and patterns of
DNFB and FA were applied to the skin in a 2-week period;
DNFB was given four times and FA was given either with the
DNFB or daily. The
tumor response to
DNFB was completed by 8 weeks from the first dose and was consistent with a dose-squared relationship. FA was not tumorigenic alone; when given with
DNFB, it caused only a small reduction in
inflammation and
tumor yield. When given daily, FA increased ulcerative skin damage,
inflammation, and the yield
tumors. The results suggest that
tumorigenesis by
DNFB, in the high-dose short-term regimen used here, is mainly due to its cytotoxicity and not contact sensitization.