Reduced ultraviolet-induced DNA damage and apoptosis in human skin with topical application of a photolyase-containing DNA repair enzyme cream: Clues to skin cancer prevention

Abstract

Abstract. The exposure of human skin to ultraviolet radiation (UVR) results in the formation of DNA photolesions that give rise to photoaging, mutations, cell death and the onset of carcinogenic events. Photolyase (EC 4.1.99.3) is a DNA repair enzyme that reverses damage caused by exposure to UVR. We sought to investigate whether addition of photolyase enhances the protection provided by a traditional sunscreen (SS), by reducing the in vivo formation of cyclobutane-type pyrimidine dimers (CPDs) and UVR-induced apoptosis in human skin. Ten volunteers (Fitzpatrick skin type II) were exposed to solar-simulated (ss) UVR at a three times minimal erythema dose for 4 consecutive days. Thirty minutes prior to each exposure, the test materials [vehicle, SS (sun protection factor 50) alone, and SS plus photolyase from Anacystis nidulans] were applied topically to three different sites. One additional site was left untreated and one received ssUVR only. Biopsy specimens were taken 72 h after the last irradiation. The amount of CPDs and the extent of apoptosis were measured by ELISA. Photolyase plus SS was superior to SS alone in reducing both the formation of CPDs and apoptotic cell death (both P<0.001). In conclusion, the addition of photolyase to a traditional SS contributes significantly to the prevention of UVR-induced DNA damage and apoptosis when applied topically to human skin.

Identification of Cyclobutane Pyrimidine Dimer-Responsive Genes Using UVB-Irradiated Human Keratinocytes Transfected with In Vitro-Synthesized Photolyase mRNA

“…This enzyme functions in diverse organisms from bacteria to vertebrates but is absent in placental mammals, including humans, that must rely solely on the less potent NER to repair UV-induced DNA lesions [ 16 ]. Sunscreen lotions containing liposomal-encapsulated bacterial photolyase or CPD-specific endonuclease have been marketed for preventing UV-induced skin damages [ 17 ], especially in patients with NER-deficiency [ 18 ].…”

DNA repair enzymes in sunscreens and their impact on photoageing—A systematic review

“…Clinical trials in 2000 12 and 2011 5 found that the addition of CPD photolyase to conventional sunscreens contributes significantly to the reduction of UV‐R‐induced DNA damage and apoptosis when applied topically to human skin. The number of UV‐B radiation‐induced CPD decreased by 40%‐45%, which demonstrates the ability of photolyase to actively repair damage 12 .…”

“…DNA damage represents one of the main causative factors of photoageing and is predominantly attributable to ultraviolet‐radiation (UV‐R) 2,5‐7 . Strategies to prevent or minimize photoageing include protection against UV‐R and preservation of antioxidant homoeostasis 3 .…”

Review of Clinical Evidence over 10 Years on Prevention and Treatment of a Film-Forming Medical Device Containing Photolyase in the Management of Field Cancerization in Actinic Keratosis

“…The studies by Stege et al [ 45 , 46 ] demonstrating that in human subjects topical applications of photolyase entrapped in liposomes penetrate the skin and reverse UV-induced CPDs, the pilot study by Puig et al [ 31 ] showing that Eryfotona AK-NMSC improved field cancerization significantly better than a comparator sunscreen SPF 100+, and the study by Berardesca et al [ 56 ] showing that an SPF 50 sunscreen plus photolyase was more effective than SPF 50 sunscreen alone in reducing UV-induced CPDs support that the clinical effects of Eryfotona AK-NMSC are related to photolyase activity and not simply ascribed to the degree of photoprotection.…”