使用尿素刺激并通过重复施用12-O-月桂醇酸-13-醋酸酯（TPA）促进的小鼠中产生的乳头瘤数量，通过在尿素给药前2 4小时一次性使用TPA处理皮肤可增加至少四倍。相比之下，TPA处理仅将癌症发生率增加了两倍。根据潜在恶性转化的差异，比较两个方案中发展出的个体乳头瘤的rasHa基因的激活。发现了一个激活的oncogene，它转化了3T3细胞，并且在从尿素激发的TPA促进的小鼠的五个乳头瘤中的四个以及类似促进的小鼠曝露于尿素之前时的十一个乳头瘤中的八个的DNA中。肿瘤或3T3灶的DNA进行南方分析表明，通过在所有突变等位基因的第二个密码子61处发生A→T转变激活了rasHa基因。因此，两个方案诱导的肿瘤在rasHa激活方面没有区别。

The number of papillomas that develop in mice initiated with a single exposure to urethane and promoted by repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) is increased greater than 4-fold by pretreating the skin once with TPA 24 hr before administration of urethane. In contrast, the carcinoma incidence was increased only 2-fold by the TPA pretreatment. Individual papillomas developed from the two protocols, differing in the potential for conversion to malignancy, were compared for activation of the rasHa gene. An activated oncogene that transformed 3T3 cells was found in the DNA of four of five papillomas from urethane-initiated, TPA-promoted mice and in eight of eleven papillomas from similarly promoted mice exposed to TPA before urethane initiation. Southern analysis of DNA from tumors or 3T3 foci demonstrated that the rasHa gene was activated by an A----T transversion at the second base of codon 61 in all mutated alleles. Thus, tumors induced by the two protocols did not differ in rasHa activation.