Revisiting the photochemistry of solar UVA in human skin

Abstract

The UV portion of sunlight has traditionally been divided into three wavelength spectra: UVC (290 nm and below), UVB (290–320 nm), and UVA (320 nm-visible). The boundaries between these three ranges are somewhat arbitrary, but the divisions have been convenient for categorizing the response of human skin to solar exposure. Wavelengths <290 nm (UVC) are blocked by stratospheric ozone but include the peak absorption of nucleic acids. Because near-monochromatic UVC (254 nm) is emitted by low-pressure mercury germicidal lamps, these wavelengths have been the historical mainstay of DNA damage and repair studies until the more recent use of longer-wavelength “more relevant” UV sources. Solar UVB contains the shortest wavelengths that penetrate the ozone layer and are absorbed by nucleic acids and, thus, constitute the greatest threat to humans, inducing erythema (sunburn), DNA damage, and ultimately skin cancer. DNA absorbs energy from both UVC and UVB, and a small proportion is converted into covalent dimer photoproducts between adjacent pyrimidine bases. It is widely believed that these lesions are the sites of the sunlight-induced “signature” mutations associated with the initiation of carcinomas (1). Like the shorter-wavelength spectra, UVA is carcinogenic (2) and is even suggested to be of greater relative importance than UVB for melanoma formation (3). However, because the amount of UVA energy absorbed by DNA is several orders of magnitude lower than UVB (4), its mechanism of action is thought to be different from UVB, proceeding by secondary free radical pathways rather than by direct absorption. Thus, until recently, the role of oxidative damage in DNA has been considered paramount in UVA carcinogenesis and UVA-associated pathologies. Recent work from the laboratory of Thierry Douki in Grenoble, culminating in the paper by Mouret et al. in this issue of PNAS (5) and in the 2006 New Investigator Award from the American Society for Photobiology, promises to foster a major change in perspective and a re-evaluation of the importance of UVA in human health and its mechanism of action on human tissues.