An in vitro strategy to evaluate the phototoxicity of solar UV at the molecular and cellular level: application to photoprotection assessment.
Skin cancers are among the most common human cancers and have an increasing incidence. The ultraviolet radiation components of sunlight play a major role in skin tumor induction and development. Cellular DNA has been identified as a target for most of the biological effects of UV, and the induction of photodamage is considered as the initiating step of photocarcinogenesis. Thus, effective photoprotection of DNA against harmful overex-posure to solar UV is a critical issue. The efficiency of a sunscreen is usually tested with respect to its ability to prevent skin erythema, but conceivably, more data are required at the molecular and cellular level in order to ascertain protection against photocarcinogenic risk. In the present study, we define a strategy based on the use of various in vitro models and solar-simulated light to evaluate photodamage and photoprotection: -Supercoiled circular plasmid DNA for detection of structural alterations. -The yeast Saccharomyces cerevisiae to evaluate cytotoxicity and genotoxicity. -The single-cell gel electrophoresis or comet assay to determine DNA damage and DNA repair in human keratinocytes. -p53 expression as a hallmark for genotoxic stress. -Induction of pigmentation in human melanocytes. In conditions where light source, spectrum and control of radiation delivery were precisely defined, we have demonstrated that the wide spectrum UVA sunscreen Mexoryl  SX protects from the cytotoxicity and genotoxicity of solar UV.
Marrot
L
L
L'Oreal Advanced Research, Life Sciences Research, Central Department of Product Safety, 1, av. E.-Schueller, 93600 Aulnay-sous-Bois, France.
Belaidi
J P
JP
Chaubo
C
C
Meunier
J R
JR
Perez
P
P
Agapakis-Causse
C
C
D015153:Blotting, Western; D001892:Camphanes; D002164:Camphor / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016923:Cell Death / Q000528:radiation effects; D002470:Cell Survival; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D004272:DNA, Mitochondrial / Q000032:analysis / Q000528:radiation effects; D017484:Dermatitis, Phototoxic / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D004586:Electrophoresis; D006801:Humans; D008544:Melanocytes / Q000187:drug effects / Q000528:radiation effects; D008698:Mesylates / Q000008:administration & dosage*; D008938:Mitosis / Q000528:radiation effects; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000528:radiation effects; D012680:Sensitivity and Specificity; D012867:Skin / Q000166:cytology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control; D013451:Sulfonic Acids; D013473:Sunscreening Agents / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014466:Ultraviolet Rays / Q000009:adverse effects*
D001892:Camphanes; D004272:DNA, Mitochondrial; D008698:Mesylates; D013451:Sulfonic Acids; D013473:Sunscreening Agents; D016159:Tumor Suppressor Protein p53; C075352:terephthalylidene dicamphor sulfonic acid; D002164:Camphor