The primary risk factor for malignant melanoma, the most deadly form of skin cancer, is exposure to ultraviolet light. The most damaging type of ultraviolet radiation is generally thought to be the lowest wavelength (and thus highest energy) radiation, known as UVB (wavelengths 290-320nm).

However, by far the most abundant type of ultraviolet radiation in the sun's rays is the lower-energy UVA1 (wavelengths 340-400nm). This is the main type of radiation used in both phototherapy and sun-beds. Some experiments in animal models have shown that UVA1 radiation also induces skin lesions, and this has led to the suggestion that it too is carcinogenic in humans.

The mechanism through which UVB radiation induces skin damage involves its absorption by DNA and the consequent formation of DNA lesions, specifically cyclobutane pyrimidine dimers: either dimers of thymine (TTs) or pyrimidine (6-4)

pyrimidone photoproducts (6-4PPs). Usually, these are repaired through the DNA excision repair pathway, but when this breaks down the characteristic mutations found in melanoma (CàT or CCàTT) can be formed. Although there is some evidence that a similar mechanism may occur with UVA1 radiation, its mutagenic effects have generally been linked to the formation of reactive oxygen species.

Angela Tewari and her colleagues from St. John's Institute of Dermatology, King's College London, UK have now compared the DNA lesions induced by UVA1 radiation with those formed after UVB radiation exposure. The researchers irradiated different patches of previously unexposed skin from healthy volunteers with both broad spectrum UVA1 and monochromatic UVB (wavelength 300nm) radiation.

The minimum dose of each radiation type necessary to induce superficial erythema (redness of the skin), known as the MED, was recorded for each subject; no intra-individual correlation was observed between the MEDs for UVA1 and UVB. The mean MED for three individuals (30.0 mJ cm-2 for UVB and 48.8 J cm-2 for the lower-energy UVA1) was calculated and used to define the doses used in the later parts of the experiment.

Six participants were given doses of 0.5, 1.5 and 3 mean MEDs of each radiation, with skin biopsies obtained immediately afterwards under local anaesthetic (the "dose-response" cohort); a further six were given a dose of 3 mean MEDs of each radiation and biopsies taken at three time points within 48 hours of exposure (the "time-course" cohort).

Tewari and her colleagues found that both UVA1 and UVB radiation induced the formation of thymidine dimers (TTs) in epidermal DNA in all volunteers immediately after exposure, whereas only UVB radiation induced the formation of pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). UVB exposure induced the formation of over four times as many TTs as an equivalent dose of UVA1. DNA repair took place consistently in all volunteers in the time-course cohort.

All the UVB-induced 6-4PPs and most of the UVA1-induced TTs were repaired within 48 hours of exposure. UVB-induced TTs were repaired at the same rate as those induced by UVA1, but significant numbers remained after 48 hours simply because more had been formed. Interestingly, the level of TTs induced by UVA1 increased with epidermal depth, compared to a decrease with epidermal depth observed with UVB-induced TTs.

The similar repair rates observed for TTs induced by both radiation types suggests that this takes place through the same mechanism. Little is known, however, about the mechanism through which UVA1 radiation originally induces the formation of TTs. Tewari and her colleagues suggest that the lack of correlation between the minimum dose of each radiation type needed to induce erythma in each individual indicates that this occurs through different mechanisms.

Although further research is needed, these results imply that UVA1 may be more carcinogenic than many people have assumed and that it would be useful to adapt commercial sunscreens to protect against a ultraviolet radiation with a broader range of wavelengths.

Reference

Tewari, A., Sarkany, R.P. and Young, A.R. (2011). UVA1 Induces Cyclobutane Pyrimidine Dimers but Not 6-4 Photoproducts in Human Skin In Vivo. J. Invest. Dermatology, published online ahead of print 6 October 2011. doi:10.1038/jid.2011.283