Effects of anti-promoters and strain of mouse on tumor promoter-induced oxidants in murine epidermal cells.

The induction of oxidant production in mouse epidermal cells by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) can be suppressed by many, but not all, known inhibitors of mouse skin tumor promotion. Members of the anti-oxidant category that were tested were ranked in the following order, 7,8-benzoflavone greater than butylated hydroxyanisole greater than ascorbic acid. In the retinoid category, retinoic acid was only moderately effective, while the trimethoxymethylphenyl analog had at least twice the inhibitory activity. Among the six protease inhibitors examined, tosylphenylalanine chloromethylketone and tosyllysine chloromethylketone were effective in diminishing the response while tosylarginine methylester, antipain, leupeptin and soybean trypsin inhibitor were ineffective, suggesting that proteases are probably not involved in the oxidant response. Several agents, trifluoperazine, trisialoganglioside and diolein, that have been shown to suppress TPA activity in other cell systems were also found to suppress the oxidant response. Finally, the extent of the oxidant response was found to correlate with sensitivity to TPA tumor promotion among the three strains of mice tested: SSIn greater than SENCAR greater than C57BL/6J.