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With the advancing widespread use of photodynamic therapy, questions have arisen about the necessity to protect the adjacent healthy skin from high-dose long-wave light. The aim of the present study was to investigate the effects of high dose visible light on the skin of healthy volunteers with focus on apoptosis, DNA damage, inflammation, melanogenesis and induction of matrix metalloproteinases (MMP). Fourteen healthy volunteers were included and irradiated daily on their buttocks with 1300 kJ/m2 long wave visible light (560-780 nm) on five consecutive days with a cumulative dose of 6500 kJ/m2. In each volunteer six biopsies were taken before and 24 h after irradiation on days 1, 2, 3 and 5 and on day 8 and 12. Frozen and paraffin sections were investigated by measuring parameters for photodamage (apoptosis, p53, phosphorylated c-Jun), skin ageing (phosphorylated c-Jun, MMP-1, elastin content) melanogenesis (Melan A). Although no sunburn cells were seen, a significant increase in perinuclear vacuolization was noted (P0.0003) from day 5 till 7 days after the last irradiation. There was no expression of phosphorylated c-Jun, whereas the expression of p53, Melan A, MMP-1 and elastin content did not change. High-dose visible light induces a significant increase in perinuclear vacuolization, but does not result in apoptosis, photodamage or early induction of skin ageing.