The time of onset and duration of 5-methoxypsoralen photochemoprotection from UVR-induced DNA damage in human skin.
Sites of previously unexposed buttock skin of eight human volunteers (skin type II) were treated daily for 3, 5, 8, or 10 days with suberythemogenic doses of solar-simulated radiation (SSR) in the presence of a UVB sunscreen containing 5-methoxypsoralen (5-MOP) at 30 p.p.m., or daily for 10 days with SSR+the same sunscreen without 5-MOP. One week after cessation of treatment, these sites, together with a control unexposed site, were challenged with 2 minimal erythema doses (2 MED) of SSR. Biopsy samples were taken within 15 min of the challenge dose, and were incubated for 1 h in tritiated thymidine. UV-induced DNA damage was measured indirectly by unscheduled DNA synthesis (UDS), and directly using a monoclonal antibody to thymine dimers, and automated image analysis. The level of pigmentation was assessed in sections in a semiquantiative fashion with Masson-Fontana staining, and the number of layers in the stratum corneum was used to assess changes in epidermal thickness. Using the UDS and dimer measurements, the level of photochemoprotection afforded by 5-MOP was determined from the reduction in the level of DNA damage observed. The photochemoprotection was expressed as a ratio of the 5-MOP-treated sites compared with the sites that did not receive 5-MOP treatment. The onset of 5-MOP photochemoprotection was shown to occur after three to five daily exposures, and became maximal after eight daily exposures. The onset of this protection coincided with increases in melanin and in stratum corneum thickness. In an extension of this study, it was found that following 10 daily exposures, 5-MOP photochemoprotection declined at a rate of about 5% per week, and in spite of several cycles of epidermal cell replacement, some protection still persisted up to 14 weeks after the end of the tanning protocol. The sites treated with sunscreen without 5-MOP was good correlation between the photochemoprotection endpoints of UDS and thymine dimer levels. The importance of 5-MOP photochemoprotection in the risk-benefit assessment of sunscreens used in suntanning is discussed.
Chadwick
C A
CA
CRG Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, U.K.
Potten
C S
CS
Cohen
A J
AJ
Young
A R
AR
D000078223:5-Methoxypsoralen; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D006801:Humans; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D012880:Skin Pigmentation; D013471:Sunburn / Q000517:prevention & control; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000078223:5-Methoxypsoralen; D004247:DNA; D008730:Methoxsalen