DNA Repair Enzymes: An Important Role in Skin Cancer Prevention and Reversal of Photodamage‑ A Review of the Literature

March 2015 | Volume 14 | Issue 3 | Original Article | 297 | Copyright © March 2015


Yasmeen Kabir MD,a Rachel Seidel BA,b Braden Mcknight BS,c Ronald Moy MDc

aDepartment of Internal Medicine, UCLA-OV/Cedars-Sinai, Los Angeles, CA
bGeorgetown University, School of Medicine, Washington, DC
cKeck School of Medicine of USC, Los Angeles, CA

Abstract
The incidence of skin cancer continues to increase annually despite preventative measures. Non-melanoma skin cancer affects more than 1,000,000 people in the United States every year.1 The current preventative measures, such as sunscreens and topical antioxidants, have not shown to be effective in blocking the effects of UV radiation based on these statistics. The level of antioxidants contained in the majority of skin creams is not sufficient to majorly impact free radical damage. Sunscreens absorb only a portion of UV radiation and often are not photostable. In this review article, we present the novel use of exogenous DNA repair enzymes and describe their role in combating photocarcinogenesis and photoaging. Topical application of these enzymes serves to supplement intrinsic DNA repair mechanisms. The direct repair of DNA damage by endogenous repair enzymes lessens rates of mutagenesis and strengthens the immune response to tumor cells. However, these innate mechanisms are not 100% efficient. The use of exogenous DNA repair enzymes presents a novel way to supplement intrinsic mechanisms and improve their efficacy. Several DNA repair enzymes critical to the prevention of cutaneous malignancies have been isolated and added to topical preparations designed for skin cancer prevention. These DNA repair enzymes maximize the rate of DNA repair and provide a more efficient response to carcinogenesis.

J Drugs Dermatol. 2015;14(3):297-301.

INTRODUCTION

More than 1,000,000 people are affected by non-melanoma skin cancer in the United States every year.1 Despite efforts to raise awareness and teach preventative measures such as sun avoidance, application of full-spectrum sunscreens and use of antioxidant creams, the incidences of both melanoma and non-melanoma skin cancers continue to increase annually and are estimated to be comparable to the sum of all other cancers combined. Given these statistics, it is clear that current preventative measures against skin cancer are insufficient. In fact, neither sunscreens nor topical antioxidants have been shown to effectively block the effects of UV radiation. The level of antioxidants contained in the majority of skin creams is too low to have a major impact on free radical damage. Sunscreens absorb only a portion of UV radiation and many fail to be photostable following a few minutes of sun exposure.2 Furthermore, observational studies have repeatedly found sunscreen use to be associated with higher risk of cutaneous melanoma and basal cell skin cancer. This correlation is hypothesized to exist because sunscreens delay the appearance of sunburn, encouraging prolonged sun exposure and thereby increasing skin cancer risk.2
It has long been known that chronic exposure to UV radiation leads to DNA damage. This process underlies photoaging, a term that broadly encompasses changes in the skin associated with life-long exposure to the sun: wrinkling, skin laxity, erythema and hyperpigmentation. More important clinically is the well-documented role of DNA damage as the inciting event in mutagenesis and tumor development.
Excessive UV radiation leads to DNA damage through several mechanisms, both direct and indirect. When irradiated, the DNA of epidermal keratinocytes forms cyclobutane pyrimidine dimers (CPDs) and 6-pyrimidine-4-pyrimidones (6-4 PPs).3 In addition, UV radiation triggers the production of oxygen radicals that alter the structure of nucleotides. These lesions, if not repaired, undermine the accuracy of DNA replication. 4 The end result is an accumulation of mutations that form the basis of tumor development.5
Though endogenous repair mechanisms exist to remove DNA lesions and damaged bases, these processes are not 100% efficient, allowing some damage to escape. Moreover, studies have
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