(A and B) Fifteen DMBA-treated D6-deficient (KO) or WT mice received TPA for 24 weeks according to protocols shown. Total papillomas and papillomas greater than 5 mm in diameter were counted once a week. Fraction of papilloma-free mice (left) and mean tumor burden per mouse (right) are shown. Log-rank tests were applied to data in left panel. See Results for results of statistical tests on tumor burden data. (C–F) D6-deficient and WT mice were treated with TPA on days 1, 5, and 10, and skin was harvested 2 or 4 days later and scored for skin thickness (dermis plus epidermis) (C), Ki67⁺ keratinocytes (basal and suprabasal layers) (D), epidermal CD3⁺ T cells (E), and MCs (F). Dorsal skin of “carrier” control mice was harvested 2 days after application of carrier (acetone) and similarly assessed. (C, E, and F) A total of 25–40 data points collected from stained sections from 5 TPA-treated mice or 4–5 carrier controls of each genotype per time point. (D) The number of Ki67⁺ cells per millimeter was determined by counting 5 randomly selected 400-μm regions of epidermis from stained sections from 5 TPA-treated mice or 4–5 carrier controls of each genotype per time point. Data are representative of 3 repeated experiments and were analyzed using a 2-tailed unpaired Student’s t test. (G) Seven D6-deficient and WT mice were treated with TPA on days 1, 5, and 10, skin was harvested 2 days later, chemokine concentrations in eluates were determined using Luminex technology, and data were analyzed using a 2-tailed unpaired Student’s t test. A repeat experiment generated a similar result. hpf, high-powered field. *P < 0.001; ^†P < 0.01.