Figure 3.

Skin tumor induction by DMBA-TPA treatment. A, Papillomas induced by DMBA-TPA treatment in Mrad1^+/+ mouse skin (left) and treated Mrad1^+/- mouse skin (right). B, Incidence of papilloma-free mice after DMBA-TPA treatment. Kaplan-Meier plot of tumor-free state as a function of time after DMBA painting followed by TPA treatment (blue, Mrad1^+/+; red, Mrad1^+/-). Mrad1^+/+ and Mrad1^+/- mice (n = 38) were initially treated once with DMBA at week 1 on the skin topically starting at ages 7 to 8 weeks, and TPA twice weekly for 17 weeks. There was a significant difference in papilloma formation between Mrad1^+/+ and Mrad1^+/- mice (P = 0.003). C, Average numbers of papillomas on each mouse (blue, Mrad1^+/+; red, Mrad1^+/-). Only papillomas larger than 1 mm diameter were counted. There was a significant difference in the number of papillomas per mouse between two the genotypes at the 17-week end point (P = 0.010). D, Size distribution of papillomas. The length of a papilloma was used to represent its size. E, H & E staining for papillomas. A typical papilloma was shown, with connective tissues extending into the tumor. F, Keratin 14 staining for keratinocytes. The same tumor sample in E was also stained for Keratin 14, and it was thus shown to be derived from keratinocytes.