Diminution of mouse epidermal superoxide dismutase and catalase activities by tumor promoters.
Diminution of mouse epidermal superoxide dismutase and catalase activities by tumor promoters.
复制标题
肿瘤促进剂降低小鼠表皮超氧化物歧化酶和过氧化氢酶活性。
作者：
Virendra Solanki;Rajendra S. Rana;Thomas J. Slaga
检测佛波酯类促癌剂及相关化合物对超氧化物歧化酶和过氧化氢酶的影响。用2微克12-O-十四酰佛波醇-13-乙酸酯(TPA)处理成年小鼠皮肤，可使皮肤表面超氧化物歧化酶和过氧化氢酶活性的基础水平持续下降。SOD活性在用药后3h内出现下降，以16~17h效果最好，同时伴随着表皮过氧化氢酶活性的下降。这两种酶的变化是在蛋白质合成增强的高背景下发生的，这表明TPA对SOD和过氧化氢酶具有选择性。其他肿瘤促进剂，如佛波醇12，13-二丁酸酯和非佛波醇肿瘤促进剂安替比林也降低了这两种酶的活性。Mezerein是一种树脂醇衍生物，促进活性较弱，但对Stage-II有很强的促进作用，似乎比TPA更有效地降低基础水平。这些结果表明，由于低水平的SOD和过氧化氢酶活性导致自由基的积累，TPA处理的小鼠皮肤可能会发生有利于肿瘤进展的损伤。此外，维甲酸、氟喹诺酮丙酮、对甲苯磺酰氨基-2-苯乙基氯甲基酮或丁基羟基甲苯都不能阻止TPA引起的超氧化物歧化酶和过氧化氢酶水平的下降，这表明这些药物抑制肿瘤的促癌作用不是通过改变酶活性来降低自由基浓度的。
The effects of phorbol ester tumor promoters and related compounds on superoxide dismutase (SOD) and catalase were examined. The treatment of adult mouse skin with 2 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a sustained decrease in the basal levels of both SOD and catalase activities in the epidermis. A decline in SOD activity occurred within 3 h after application and the maximum effect was seen at 16--17 h. The decrease in SOD activity was always accompanied by a similar decline in the epidermal catalase activity. The alterations in both enzymes occurred against a high background of enhanced protein synthesis which indicates that the effect of TPA is selective for SOD and catalase. Other tumor promoters such as phorbol 12,13-dibutyrate and the non-phorbol tumor promoter anthraline also lowered the activities of both the enzymes. Mezerein, a resiniferonol derivative with weak promoting activity but a potent stage-II promoter, appeared to be more potent than TPA in lowering the basal levels. These results indicate that damage which favors neoplastic progression could occur in TPA-treated mouse skin due to the accumulation of free radicals resulting from low levels of SOD and catalase activity. In addition, the TPA-caused decrease in the levels of SOD and catalase was not prevented by either retinoic acid, fluocinolone acetonide, tosyl amino-2-phenylethyl chloromethyl ketone, or butylated hydroxytoluene, suggesting that inhibition of tumor promotion by these agents is not mediated through alterations in the levels of enzymatic activities which decrease free radical concentrations.