T4 endonuclease V: review and application to dermatology.
BACKGROUND
T4 endonuclease V was originally isolated from Escherichia coli infected with T4 bacteriophage. It has been shown to repair ultraviolet (UV)-induced cyclobutane pyrimidine dimers in DNA, which, when unrepaired, contribute to mutations that result in actinic keratoses and non-melanoma skin cancers (NMSC). This is a particular concern in patients with genetic defects in their DNA repair systems, especially those with xeroderma pigmentosum (XP). When packaged in liposomes and applied topically, T4 endonuclease V can traverse the stratum corneum and become incorporated within the cytoplasm and nucleus of epidermal keratinocytes and Langerhans cells.


OBJECTIVE
To review all major studies evaluating the efficacy of T4 endonuclease V in animals and humans, the toxicity and safety profile of the topical medication and its potential clinical uses.


METHODS
A literature search was performed through PubMed/Medline, using the keywords 'T4N5', 'T4 endonuclease V' and 'dimericine'. Papers found in the bibliographies of those identified in the initial search and deemed relevant were also included.


CONCLUSIONS
This enzyme increases the repair of UV-damaged DNA and produces other beneficial effects on UV-damaged cells. In clinical trials in XP patients, topical application of liposome-encapsulated T4 endonuclease V reduced the incidence of basal cell carcinomas by 30% and of actinic keratoses by > 68%. Adverse effects were minimal, and there was no evidence of allergic or irritant contact dermatitis. Although the photoprotective effect of T4N5 has been investigated only in XP patients, the possibility exists that it may benefit others likely to develop premalignant keratoses and NMSC, such as organ transplant recipients receiving immunosuppressive therapy and individuals who have had numerous psoralen plus UVA photochemotherapy treatments. It may be also be effective for normal individuals.
Cafardi
Jennifer A
JA
University of Alabama at Birmingham, Department of Dermatology, USA.
Elmets
Craig A
CA
D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D017122:Bacteriophage T4 / Q000201:enzymology; D002280:Basal Cell Carcinoma / Q000209:etiology / Q000517:prevention & control; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000517:prevention & control; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004260:DNA Repair / Q000187:drug effects; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000517:prevention & control; D010787:Photosensitivity Disorders / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D011740:Pyrimidine Dimers; D051381:Rats; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control; D013471:Sunburn / Q000517:prevention & control; D014764:Viral Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000188:drug therapy / Q000201:enzymology
D008081:Liposomes; D011740:Pyrimidine Dimers; D014764:Viral Proteins; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer)