Topical Formulation Engendered Alteration in p53 and Cyclobutane Pyrimidine Dimer Expression in Chronic Photodamaged Patients

March 2013 | Volume 12 | Issue 3 | Original Article | 336 | Copyright © March 2013

James M. Spencer MD MS,a Summer D. Moon BS,b Kara M. Trapp BA,c and Michael B. Morgan MDd-f

aDepartment of Dermatology, Mount Sinai School of Medicine, New York, NY bLake Erie College of Osteopathic Medicine, Bradenton, FL cGeorgetown University School of Medicine, Washington, DC dDepartment of Pathology, University of South Florida Morsani College of Medicine, Tampa, FL eDepartment of Dermatology, Michigan State University, East Lansing, MI fBay Area Dermatopathology, Tampa, FL

While the clinical attributes of photoaging are well characterized in the literature, the pathogenic mechanisms that underlie these changes are incompletely elucidated. At the molecular level, p53 tumor-suppressor gene product mediated excision repair of ultraviolet (UV)-induced DNA damage is a critical effector in xeroderma pigmentosum (XP) and potentially in conventional photoaging. We examined p53 activity and measured UV-induced DNA damage via cyclobutane pyrimidine dimers (CPDs) quantitatively in 20 volunteers before and after an 8-week, open-label prospective topical application of a proprietary DNA recovery serum (Celfix). There was a statistically significant decrease in immunohistochemically determined p53 and CPD levels. While these data are preliminary, the findings lend support to the theoretical possibility of a topical agent reversing the effects of photodamage at the molecular level and, potentially, an ameliorative outcome clinically.

J Drugs Dermatol. 2013;12(3):336-340.


The development of skin cancer and the exacerbation of skin aging due to ultraviolet light radiation (UVR) exposure in individuals is well documented in the scientific and medical literature.1-5 The process of skin aging is influenced by a combination of intrinsic and extrinsic factors that result in deleterious effects on human skin.6,7 While intrinsic skin aging has been considered an irreversible process, extrinsic skin aging may exhibit a reversal upon nucleotide excision repair (NER) of ultraviolet (UV)-induced DNA damage. The DNA lesions induced by UV light include cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs).8 The efficiency of NER in removing CPDs and 6-4PPs is largely dependent on the function of the p53 tumor-suppressor gene.9 The likely mechanism through which p53 contributes to NER is based on its role in the transcriptional regulation of downstream effector genes involved in the global genomic repair (GGR) subpathway of NER.10 In addition to the GGR subpathway, at least one additional subpathway, the transcription-coupled repair (TCR) subpathway of NER, has been demonstrated in the scientific literature. 11 GGR represents the repair of DNA lesions in transcribed
and nontranscribed strands of the genome, whereas TCR represents a backup system to repair lesions that are slowly repaired or not repaired by GGR in transcribed strands. The significance of NER in the prevention of skin cancer development can be observed in individuals with xeroderma pigmentosum (XP) who have mutations in NER genes and exhibit a 1,000-fold increased susceptibility to UV-induced skin cancer.12
In addition to the NER pathway, UV-induced DNA damage is repaired by the action of photolyase enzymes, which bind CPDs and 6-4PPs and use the energy of visible light to revert pyrimidine dimers back into their monomer forms.13 Although photolyases represent a highly conserved repair system with an early evolutionary history, humans do not possess endogenous photolyase activity and must rely exclusively on the NER pathway.14
In the present study, we evaluated the efficacy of a topical formulation containing photolyase and 2 additional DNA repair enzymes in reverting photodamage and reducing the effects of skin aging. Together with photolyase from Anacystis nidulans,