After sun reversal of DNA damage: enhancing skin repair.
UV-induced DNA damage has been directly linked to skin cancer, and DNA repair is an important protection against this neoplasm. This is illustrated by the genetic disease xeroderma pigmentosum wherein a serious defect in DNA repair of cyclobutane pyrimidine dimers dramatically increases the rate of skin cancer. In other instances in which skin cancer rates are elevated, deficits in DNA repair may also be one of the causal factors. For example, solid organ transplant patients have elevated rates of skin cancer that are correlated with the dose and length of exposure to immunosuppressive drugs (predominantly cyclosporine A (CsA) and ascomycin (FK506)-related tacrolimus). We have found that treatment of cultured epidermal cells with CsA or ascomycin inhibits their removal of DNA damage by about 20% at 24 h. In a further example, people with a polymorphism in the DNA repair gene 8-oxo-guanine glycosylase (OGG1) have an increased risk of skin cancer. We have found that the cells with this variant polymorphism have an increased sensitivity of about 20% to a broad range of cytotoxic agents. The DNA deficits caused by immunosuppressive drugs or the OGG1 polymorphism can be overcome by the delivery of DNA repair enzymes in liposomes. The data suggests that deficits in DNA repair, even if they are not as severe as in the case of XP, may contribute to increased rates of cancer, and that topical therapy with DNA repair enzymes may be a promising avenue for after-sun protection.
Yarosh
Daniel B
DB
AGI Dermatics, 205 Buffalo Avenue, Freeport, NY 11520, USA. danyarosh@agiderm.com
Canning
Matthew T
MT
Teicher
Danielle
D
Brown
David A
DA
D002460:Cell Line; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects; D011110:Polymorphism, Genetic; D013472:Sunlight
D007166:Immunosuppressive Agents; D004247:DNA