880 INVESTIGATIVE REPORT
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Sub-optimal Application of a High SPF Sunscreen Prevents Epidermal DNA Damage in Vivo
Antony R. YOUNG 1, Jessica GREENAWAY 1, Graham I. HARRISON 1, Karl P. LAWRENCE 1, Robert SARKANY 1, Thierry DOUKI 2, France BOYER 3, Gwendal JOSSE 3, Emmanuel QUESTEL 3, Camille MONTEIL 3 and Ana B. ROSSI 3, 4
1
King’ s College London, St John’ s Institute of Dermatology, London, UK, 2 Université Grenoble Alpes, SyMMES, & CEA, INAC, LAN, Grenoble,
3
Pierre Fabre Dermo-Cosmétique, Clinical Skin Research Center, and 4 Dermatology Department, Larrey University Hospital, Toulouse, France
The cyclobutane pyrimidine dimer( CPD) is a potentially mutagenic DNA photolesion that is the basis of most skin cancers. There are no data on DNA protection by sunscreens under typical conditions of use. The study aim was to determine such protection, in phototypes I / II, with representative sunscreen-user application. A very high SPF formulation was applied at 0.75, 1.3 and 2.0 mg / cm 2. Unprotected control skin was exposed to 4 standard erythema doses( SED) of solar simulated UVR, and sunscreen-treated sites to 30 SED. Holiday behaviour was also simulated by UVR exposure for 5 consecutive days. Control skin received 1 SED daily, and sunscreen-treated sites received 15( all 3 application thicknesses) or 30( 2.0 mg / cm 2) SED daily. CPD were assessed by quantitative HPLC-tandem mass spectrometry( HPLC-MS / MS) and semi-quantitative immunostaining. In comparison with unprotected control sites, sunscreen significantly( p ≤ 0.001 – 0.05) reduced DNA damage at 1.3 and 2.0 mg / cm 2 in all cases. However, reduction with typical sunscreen use( 0.75 mg / cm 2) was non-significant, with the exception of HPLC-MS / MS data for the 5-day study( p < 0.001). Overall, these results support sunscreen use as a strategy to reduce skin cancer, and demonstrate that public health messages must stress better sunscreen application to get maximal benefit.
Key words: sunscreen; photoprotection; DNA protection; cyclobutane pyrimidine dimers.
Accepted Jun 14, 2018; Epub ahead of print Jun 25, 2018 Acta Derm Venereol 2018; 98: 880 – 887.
Corr: Antony R Young, King’ s College London, 9 th Floor, Tower Wing, Guy’ s Hospital, London SE1 9RT, UK. E-mail: antony. young @ kcl. ac. uk
SIGNIFICANCE
Skin cancer is an increasing public health burden in many countries. Most skin cancers are caused by DNA damage from ultraviolet radiation in sunlight. This study shows that a very high sun protection factor sunscreen can inhibit DNA damage in the skin caused by high doses of artificial sunlight, even when the sunscreen is used less than optimally. The data suggest that sunscreen use is likely to reduce skin cancer and that there should be more emphasis in communicating how to best use sunscreens in public health campaigns.
Solar ultraviolet radiation( UVR) causes skin cancers derived from epidermal melanocytes( melanoma) and keratinocytes( basal cell carcinoma( BCC) and squamous cell carcinoma( SCC)). Skin cancer incidence is increasing in many countries with predominantly fair-skinned populations( 1, 2). Epidemiology has shown a relationship between sunburn( erythema) and malignant melanoma( MM), especially with childhood exposure( 3). There is also evidence for such a relationship for BCC. The epidemiology for SCC supports a role for chronic low dose( sub-erythemal) solar UVR exposure( 4).
Keratinocyte cancers( KC) are initiated by UVRinduced DNA damage, in particular the cyclobutane pyrimidine dimer( CPD) that results in characteristic C to T transition mutations in key regulatory genes such as p53( 5). There is evidence for a role for such mutations in MM( 6), though its molecular pathogenesis is more complex.
Sunscreens increase the dose required to induce erythema for which their index of efficacy is the sun protection factor( SPF) that is determined by exposing the skin to solar simulated radiation( SSR) with the sunscreen applied at 2 mg / cm 2. However, sunscreens may not fully inhibit sunburn( 7, 8). This is because people typically overestimate protection indicated by the label, by using much less sunscreen than 2 mg / cm 2 with a commensurate reduction of actual SPF( 9).
Sunscreen use is widely advocated as a means of reducing skin cancer risk and this has been supported by a randomised trial of sunscreen use( SPF 16) which showed protective effects for actinic keratoses( AK)( 10), and also for SCC( 11) in a high-risk population in sub-tropical Australia. To date, there is no convincing evidence that sunscreen use has any significant impact on BCC. Metaanalyses of several case-control studies have shown no effect of sunscreen use on melanoma( 12). However, more recently, a reduction of melanoma in the same Australian study population as described above( 13) and also a large prospective population-based study reported that use of sunscreens with SPF ≥ 15 vs SPF < 15 reduced the risk of melanoma( hazard ratio 0.67( 95 % confidence interval( CI) 0.53 – 0.83) in Norway( 14). Long-term sunscreen use has also been shown to inhibit photoageing( 15).
Prospective trials for skin cancer prevention by sunscreens are complex and the International Agency for Research on Cancer( IARC) identified the need for sunscreen studies on biomarkers, such as DNA damage,
doi: 10.2340 / 00015555-2992 Acta Derm Venereol 2018; 98: 880 – 887
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica.