Fig 1.
Skin appearance after UV-B irradiation and procedure for topical treatment of skin lesions.
(A) Photographs of UV-B-irradiated mouse skin at indicated days post irradiation initiation. (B) Example of tattooed area and of the use of the chamber system to perform topical application.
Table 1.
Patients and skin lesion characteristics.
Fig 2.
Comparative histology of human and mouse UV-B-induced AK lesions.
Hematoxylin and eosin staining. Representative cases: A1) Human normal skin, case 399. A2) Human early-stage AK, case P14-1532. A3) Human early-stage AK, case P14-1358. A4) Human intermediate-stage, case P14-1363. A5) Human advanced-stage AK, case P14-1521. A6) Human advanced-stage AK, case P14-1828. B1) Mouse normal skin, case D181P14. B2) Mouse early-stage AK, case 203P21. B3) Mouse early-stage AK, case D195P16. B4) Mouse intermediate-stage, case 198P39. B5) Mouse advanced-stage AK, case 488. B6) Mouse advanced-stage AK, case D221-1. Scale bars represent 100 μm.
Table 2.
Comparative histological immunohistochemical analysis of human and mouse UV-B induced AK lesion.
Fig 3.
Phenotypic analysis of human (A) and mouse UV-B-induced (B) AK lesions. P53 and Ki67 staining.
Histological sections of normal human skin (pictures labelled “A”) and normal murine skin (pictures labelled “B”) as well as human and murine AK lesions (labelled “A” and “B” respectively) at various stages were stained with P53 (pictures with 1, 2 or 3 numbers) or Ki67 antibodies (pictures with 4, 5 or 6 numbers). Representative cases: Human, normal skin, case 399: A1) p53 staining, A4) Ki67 staining. Human, early-stage AK, case P14-1532: A2) p53 staining, A5) Ki67 staining. Human, advanced-stage AK, case P14-1521: A3) p53 staining, A6) Ki67 staining. Mouse, normal skin case D181P14: B1) p53 staining, B4) Ki67 staining. Mouse, early-stage AK, case D195P16: B2) p53 staining, B5) Ki67 staining. Mouse, advanced-stage AK, case D-221-1: B3) p53 staining, B6) Ki67 staining. Scale bars represent 100 μm.
Fig 4.
Ingenol mebutate inhibits UV-B-induced AK lesions.
Mice were exposed to UV-B irradiation for 74 days, and then topically treated for 5h with either 0.015% ingenol mebutate or control vehicle (5% DMSO, 70% Glycerol and 25% H2O) on day 78 after irradiation initiation. A) Skin appearance after ingenol mebutate treatment, at days indicated after irradiation initiation. B) Histology of UV-B-irradiated mouse skin topically treated with either control vehicle or 0.015% ingenol mebutate. B1-B2) Hematoxylin and eosin staining of control vehicle-treated skin. B3) Ki67 staining of control vehicle-treated skin. B4) p53 staining of control vehicle-treated skin. B5 and B6) Hematoxylin and eosin staining of 0.015% ingenol mebutate-treated skin. B7) Ki67 staining of 0.015% ingenol mebutate-treated skin. B8) p53 staining of 0.015% ingenol mebutate-treated skin. Experiments involved three mice per experimental group. Scale bars represent 100 μm.
Fig 5.
Comparison of macroscopic skin lesions.
Photographs taken with either a standard camera (A1-A3) or a calibrated digital dermatoscope (B1-B3). Mice were exposed to UV-B irradiation for 108 days and photographs were taken on the indicated days after irradiation initiation. Scale bars represent 500 μm.
Fig 6.
0.5% 5-FU inhibits UV-B-induced AK lesions.
Mice were exposed to UV-B irradiation for 74 days, then topically treated for 30h with either 0.05% 5-FU or control vehicle (5% DMSO, 70% Glycerol and 25% H2O), starting on day 78 after irradiation initiation. The chamber systems containing the 0.05% 5-FU cream were then removed for 20h, and mice were again treated topically for 30 additional hours. Skin appearance after either control vehicle (A) or 5-FU (B) treatment, at indicated days after treatment initiation. Scale bars represent 500 μm. C) Assessment of the number of skin lesions in control vehicle and 5-FU treated mice, before and after treatment (on day 28 after treatment initiation). Experiments involved five mice per experimental group.