Effect of ascorbic acid and its synthetic lipophilic derivative ascorbyl palmitate on phorbol ester-induced skin-tumor promotion in mice.
The effect of topical application of ascorbic acid (AA) and ascorbyl palmitate (AP) on 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion in mouse skin was investigated. A single application of TPA decreased epidermal AA by 45%. Repetitive application of 6 and 28 mumol AA with 2 nmol TPA inhibited tumor multiplicity by 39% and 76%. Repetitive application of 0.16, 0.8, and 4.0 mumol AA with 5 nmol TPA inhibited tumor multiplicity by 16%, 46%, and 91%. Because AA may be poorly absorbed cutaneously, we evaluated the effect of dietary AA. Supplementation of drinking water with AA increased epidermal ascorbic acid levels by 50%. Dietary intake of AA did not inhibit TPA-induced tumor promotion. Preliminary data suggest that the mice not receiving AA developed increased epidermal AA levels in response to the tumor promoting regimen. Recently we have found that dietary AP inhibited TPA-induced biochemical parameters associated with tumor promotion.
Smart
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Department of Toxicology, North Carolina State University, Raleigh 27695-7633.
Crawford
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D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004032:Diet; D004817:Epidermis / Q000378:metabolism; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000378:metabolism; D009994:Osmolar Concentration; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate
D004247:DNA; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid