Irradiance-dependent UVB Photocarcinogenesis

Abstract

Ultraviolet B (UVB) radiation from the sun may lead to photocarcinogenesis of the skin. Sunscreens were used to protect the skin by reducing UVB irradiance, but sunscreen use did not reduce sunburn episodes. It was shown that UVB-induced erythema depends on surface exposure but not irradiance of UVB. We previously showed that irradiance plays a critical role in UVB-induced cell differentiation. This study investigated the impact of irradiance on UVB-induced photocarcinogenesis. For hairless mice receiving equivalent exposure of UVB radiation, the low irradiance (LI) UVB treated mice showed more rapid tumor development, larger tumor burden, and more keratinocytes harboring mutant p53 in the epidermis as compared to their high irradiance (HI) UVB treated counterpart. Mechanistically, using cell models, we demonstrated that LI UVB radiation allowed more keratinocytes harboring DNA damages to enter cell cycle via ERK-related signaling as compared to its HI UVB counterpart. These results indicated that at equivalent exposure, UVB radiation at LI has higher photocarcinogenic potential as compared to its HI counterpart. Since erythema is the observed sunburn at moderate doses and use of sunscreen was not found to associate with reduced sunburn episodes, the biological significance of sunburn with or without sunscreen use warrants further investigation.

Irradiance, as well as body site and timing of readings, is important in determining ultraviolet A minimal erythemal dose: reply from the authors

“…Surprisingly, they found that low irradiance (at long exposure time) resulted in significantly increased numbers of p53 mutations and decreased apoptosis when compared with high irradiance (at short exposure time). 10 In conclusion, the irradiance dependency of the UVA1 MED may explain the differences between the 24-h MEDs observed in our study 2 and the previous investigation of Beattie et al 3 Importantly, the aforementioned statement also implies that UVA1 phototesting should be performed with the same irradiance that is used for the actual phototherapeutic treatment. 8 Otherwise a correction factor has to be applied to determine the safe UVA1 starting dosage.…”

“…However, it has been shown that the law of reciprocity does not always hold, in particular, for end points such as UV-induced erythema and certain other photobiological effects. [7][8][9][10] Thus a low irradiance, as used in our study, 2 may allow repair mechanisms and anti-inflammatory processes to keep pace with the photochemically induced damage. 8,9 Moreover, at high irradiances when the energy is delivered in a shorter period of time, a stronger heating of skin tissue may occur leading to additional thermal injury.…”

“…8,9 Moreover, at high irradiances when the energy is delivered in a shorter period of time, a stronger heating of skin tissue may occur leading to additional thermal injury. 9 Lan et al 10 reported on irradiancedependent UVB photocarcinogenesis using equivalent surfaceexposure UVB doses (200 mJ cm…”

Excimer light devices: are they really monochromatic?

“…It would be reasonable to presume that the difference in irradiance may contribute to the difference in MED. However, we had recently demonstrated that UVB‐induced erythema depends on total surface exposure dose but not irradiance using a hairless mouse model . To clarify this issue, 15 healthy volunteers were included in our follow‐up investigation regarding the relationship between UVB‐induced erythema and irradiance in human beings.…”

Different genetic mechanisms mediate spontaneous versus UVR-induced malignant melanoma

“…While the number of UVR signature mutations in MMs strongly suggests a role for UVR in MM, the number of mutations present in a MM is due to not just obvious levels of exposure, and protective and repair differences between individuals, but also other factors, for instance the type of exposure. There is in vivo evidence that less intense exposures may be more important for skin cancer induction than more intense doses which cause more apoptosis (8), and even for a single exposure there are significant differences in skin responses between the same dose (i.e. the same levels of DNA damage) administered with high intensity over a short period versus a low intensity for a longer period (9).…”