Powerful skin cancer protection by a CPD-photolyase transgene.
Curr Biol
; 15(2): 105-15, 2005 Jan 26.
Article
en En
| MEDLINE
| ID: mdl-15668165
ABSTRACT
BACKGROUND:
The high and steadily increasing incidence of ultraviolet-B (UV-B)-induced skin cancer is a problem recognized worldwide. UV introduces different types of damage into the DNA, notably cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts (6-4PPs). If unrepaired, these photolesions can give rise to cell death, mutation induction, and onset of carcinogenic events, but the relative contribution of CPDs and 6-4PPs to these biological consequences of UV exposure is hardly known. Because placental mammals have undergone an evolutionary loss of photolyases, repair enzymes that directly split CPDs and 6-4PPs into the respective monomers in a light-dependent and lesion-specific manner, they can only repair UV-induced DNA damage by the elaborate nucleotide excision repair pathway.RESULTS:
To assess the relative contribution of CPDs and 6-4PPs to the detrimental effects of UV light, we generated transgenic mice that ubiquitously express CPD-photolyase, 6-4PP-photolyase, or both, thereby allowing rapid light-dependent repair of CPDs and/or 6-4PPs in the skin. We show that the vast majority of (semi)acute responses in the UV-exposed skin (i.e., sunburn, apoptosis, hyperplasia, and mutation induction) can be ascribed to CPDs. Moreover, CPD-photolyase mice, in contrast to 6-4PP-photolyase mice, exhibit superior resistance to sunlight-induced tumorigenesis.CONCLUSIONS:
Our data unequivocally identify CPDs as the principal cause of nonmelanoma skin cancer and provide genetic evidence that CPD-photolyase enzymes can be employed as effective tools to combat skin cancer.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_skin_diseases
Asunto principal:
Dímeros de Pirimidina
/
Neoplasias Cutáneas
/
Rayos Ultravioleta
/
Daño del ADN
/
Carcinoma
/
Desoxirribodipirimidina Fotoliasa
/
Reparación del ADN
Límite:
Animals
Idioma:
En
Revista:
Curr Biol
Asunto de la revista:
BIOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Países Bajos