Iversen O H
Virchows Arch B Cell Pathol Incl Mol Pathol. 1985;49(2):129-35. doi: 10.1007/BF02912091.
In order to study a possible dose/response relationship in the tumorigenic effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), groups of hairless mice were treated topically on the back skin with different doses and treatment schedules of TPA in acetone. A group of 104 mice (56 M/48 F) received a single application of 20 nmol TPA; 80 mice (32 M/48 F) received 2 X 20 nmol TPA at 3 day intervals; 95 mice (48 M/47 F) received five applications; and 32 mice (16 M/16 F) received 50 applications of 20 nmol TPA twice weekly. Two groups of 32 mice (16 M/16 F) were painted topically on the back skin twice weekly with doses of 17 and 10 nmol TPA, respectively, in each application for 60 weeks or until the animals died. All applications were given in 0.1 ml reagent grade acetone. A control group was treated twice weekly with acetone alone for 60 weeks. Long-term application of 17 nmol TPA was toxic to the animals, and only 20% survived 10 months. Doses of 10 nmol TPA twice weekly were less toxic, and 80% of the animals survived 14 months. The other doses were fairly non-toxic. The results were assessed statistically by accepted methods for tumor rates and yields, respectively. There was a significant tumor incidence after the higher doses of TPA and a clear dose-response relationship. This further strengthens the evidence that TPA is a complete carcinogen, and not merely a promoter.
为了研究12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）致瘤作用中可能存在的剂量/反应关系，将无毛小鼠分组，用丙酮配制的不同剂量和处理方案的TPA对其背部皮肤进行局部处理。一组104只小鼠（56只雄性/48只雌性）单次涂抹20 nmol TPA；80只小鼠（32只雄性/48只雌性）每隔3天涂抹2×20 nmol TPA；95只小鼠（48只雄性/47只雌性）涂抹5次；32只小鼠（16只雄性/16只雌性）每周两次涂抹50次20 nmol TPA。两组32只小鼠（16只雄性/16只雌性）每周两次在背部皮肤局部涂抹剂量分别为17和10 nmol TPA，每次涂抹持续60周或直至动物死亡。所有涂抹均用0.1 ml试剂级丙酮。一个对照组每周两次仅用丙酮处理60周。长期涂抹17 nmol TPA对动物有毒性，10个月后仅20%存活。每周两次涂抹10 nmol TPA毒性较小，80%的动物存活14个月。其他剂量毒性相当小。分别采用公认的肿瘤发生率和产率评估方法对结果进行统计学分析。较高剂量的TPA处理后肿瘤发生率显著，且存在明显的剂量 - 反应关系。这进一步强化了TPA是一种完全致癌物而非仅仅是促癌剂的证据。
