Time course for early adaptive responses to ultraviolet B light in the epidermis of SKH-1 mice

Hairless SKH-1 mice were exposed once to UVB light (180 mJ/cm(2)), and mech anistically important early adaptive responses in the epidermis were evalua ted by immunohistochemical and morphological methods, Interrelationships in the time course for these UVB-induced responses were examined. The number of epidermal cells with DNA strand breaks (terminal deoxynucleotidyl transf erase-mediated dUTP nick end labeling-positive cells) or with thymine dimer s increased to maximal levels within 30 min after WE. The number of cells w ith DNA strand breaks located specifically in the basal layer of the epider mis was increased substantially by 3-30 min after UVB and gradually increas ed further over the next 5,5 hours. DNA strand breaks specifically in the b asal layer of the epidermis were increased maximally at 6 h after UVB. The number of epidermal cells with DNA strand breaks or thymine dimers decrease d markedly between 12 and 36 h, Pyrimidine (6-4) pyrimidone photodimers (6- 4 photoproducts) in isolated epidermal DNA were increased immediately after irradiation of the mice with UVB and decreased markedly during the next 6 h, Exposure to UVB caused a rapid I-fold increase in the number of epiderma l cells with the DNA mismatch repair protein, MSH2 (within 30-60 min), and the level of MSH2-positive cells remained elevated for at least 48 h, These observations suggest a possible role of MSH2 in the repair of UVB-induced DNA damage, The number of epidermal cells with wild-type p53 protein started to increas e at 1, h after UVB exposure and reached maximal levels by 8-12 h, The numb er of p53-positive cells fell markedly between 24 and 48 h, The time course for UVB-induced increases in the number of p53-positive cells was parallel ed very closely by the time course for WE-induced increases in the number o f cells with p21(WAF1/CIP1), increases in morphologically distinct apoptoti c sunburn cells, and decreases in the number of epidermal. cells with bromo deoxyuridine (BrdUrd) incorporation into DNA, Although the start of UVB-ind uced increases in the number of p21(WAF1/CIP1)-positive cells was similar t o that for the increase in p53-positive cells and very high levels of p21(W AF1/CIP1)-positive cells were observed at 8-12 h, maximal increases in p21( WAF1/CIP1)-positive cells were not achieved until 24 h after UVB irradiatio n (similar to 12 h after the peak value for p53), Myeloperaxidase-positive epidermal cells started to increase by 30 min after UVB exposure, and maxim al numbers of myeloperoxidase-positive epidermal cells were observed at 2 h after UVB (18-fold higher than in nonirradiated control mice). An increase d level of epidermal peroxidase enzyme activity in the epidermis was also o bserved from 1 to 24 h after exposure of the mice to WE, Although neutrophi l infiltration into the epidermis was not seen after exposure to UVB, neutr ophil infiltration into the dermis (inflammatory response) was observed fro m 4 to 144 h after UVB exposure. In contrast to the marked inhibitory effec t of UVB on BrdUrd incorporation into the DNA of epidermal cells observed a t 8-12 h after UVB irradiation (>90% inhibition), BrdUrd incorporation into the DNA of epidermal cells was markedly increased (similar to 30-fold incr ease in the number of BrdUrd-positive cells) at 48 h after WE exposure, and increases in epidermal cell layers and epidermal thickness (hyperplasia) w ere also observed. These later effects were associated with regeneration of the damaged epidermis.