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 .