Effect of tumor promoters on lipid peroxidation in mouse skin

Products of lipid peroxidation were measured in mouse epidermis. These were shown to increase with advancing age. Conversely, a decline in these products was observed on treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoting agent. A decline in lipid peroxidation occurred within 4 h after application of 2 micrograms TPA and the maximum effect was seen at 22-24 h. A lesser active tumor promoter, phorbol dibenzoate; and ethyl phenylpropiolate, a purely hyperplastic agent, also lowered lipid peroxidation; while phorbol, a non-promoter, did not show any significant effect. Mezerein, a resiniferonal derivative with weak promoting activity but a potent stage II promoter, appeared to be more potent than TPA in lowering the basal levels of peroxidation. The TPA-induced decrease in lipid peroxidation could be prevented by fluocinolone acetonide, a potent antipromoting and antimitotic agent, but not by retinoic acid and tosylamino-2-phenylethylchlorimethyl-ketone which are relatively potent antipromoting agents but lack antimitotic activity, suggesting that the decrease of lipid peroxidation by tumor promoting agents is possibly related to their mitotic activity. Furthermore, skin papilloma and carcinoma contain lower levels of lipid peroxidation compared to epidermis from the same mice.