Mechanism of skin tumorigenesis by contact sensitizers: the effect of the corticosteroid fluocinolone acetonide on inflammation and tumor induction by 2,4 dinitro-1-fluorobenzene in the skin of the TG.AC (v-Ha-ras) mouse.
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.
Albert
R E
RE
University of Cincinnati Medical Center, Department of Environmental Health, OH 45267-0056, USA.
French
J E
JE
Maronpot
R
R
Spalding
J
J
Tennant
R
R
D000818:Animals; D003877:Dermatitis, Contact / Q000150:complications*; D004139:Dinitrofluorobenzene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005446:Fluocinolone Acetonide / Q000494:pharmacology*; D011905:Genes, ras / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D005938:Glucocorticoids; D005446:Fluocinolone Acetonide; D004139:Dinitrofluorobenzene; D013755:Tetradecanoylphorbol Acetate