DNA damage in UV-irradiated human skin in vivo: automated direct measurement by image analysis (thymine dimers) compared with indirect measurement (unscheduled DNA synthesis) and protection by 5-methoxypsoralen.
The incidence of the various types of skin cancer in the general population has been increasing at an annual rate of 2-8% over the past 2 decades. In spite of considerable media coverage on the risk of skin cancer the acquisition of a suntan is still very popular. Thus the UV exposures required for tanning pose a serious carcinogenic risk, particularly to individuals who tan poorly. On the other hand, the presence of natural skin pigment, or the ability to tan easily can protect the skin against some of the harmful effects of subsequent UV exposures (Kollias et al. 1991). We have recently shown (Young et al. 1991) in human volunteers, using an indirect measurement of DNA damage (unscheduled DNA synthesis (UDS) detected by autoradiography), that a tan induced by UV in the presence of a UVB sunscreen (Parsol MCX) preparation containing 5-methoxypsoralen (5-MOP) is more effective at protecting the skin against a subsequent DNA-damaging challenge dose of UV than a tan induced by UV alone, particularly in individuals who tan poorly. No such protection was seen with the same sunscreen lacking 5-MOP. 5-MOP is an ingredient in natural citrus oils and in many other plants. Here we show the same pattern of protective action when measuring, for the first time, DNA damage directly using a monoclonal antibody to thymine dimers (a major category of DNA lesion induced by UV radiation) on fixed human skin sections and automated image analysis. There is a good correlation between UV exposure dose and the levels of thymine dimers in epidermal nuclei. The levels of thymine dimers (measured as absorption by the mean integrated optical density (IOD)) also correlated well with the levels of UDS (grains per nucleus). These findings are of importance in the comparative risk-benefit assessment of sunscreens with and without 5-MOP. The techniques described have applications for measuring other DNA lesions following UV and other exposures.
Potten
C S
CS
Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Chadwick
C A
CA
Cohen
A J
AJ
Nikaido
O
O
Matsunaga
T
T
Schipper
N W
NW
Young
A R
AR
D000078223:5-Methoxypsoralen; D004249:DNA Damage / Q000528:radiation effects*; D006801:Humans; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011740:Pyrimidine Dimers; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D012867:Skin / Q000528:radiation effects*; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers; D011837:Radiation-Protective Agents; D000078223:5-Methoxypsoralen; D008730:Methoxsalen