Ultraviolet B radiation-induced DNA lesions in mouse epidermis: an assessment using a novel 32P-postlabelling technique.
Ultraviolet B (UVB) component of the sunlight is the major cause of nonmelanoma skin cancer (NMSC) in humans. UVB is absorbed directly by cellular DNA and produces lesions that may cause mutation(s) in target gene(s) ultimately leading to cancer. Early detection of these lesions, therefore, may help to identify individuals at a high risk to develop NMSC, and devise approaches for the prevention of this common malignancy. Employing mouse skin as a model, we applied a 32P postlabelling method to detect UVB-induced DNA lesions in the epidermis in nanomole quantities. Autoradiography maps showed that epidermal DNA from UVB exposed mice at 24 h contain up to five DNA lesions; the quantitation of these lesions showed that their formation increased in a UVB dose-dependent manner. Treatment of DNA samples with the bacteriophage DNA repair enzyme T4 endonuclease V confirmed that four of these lesions are pyrimidine dimers. While, some of these lesions were repaired 18 h after UVB irradiation, 30% of them persisted even 48 h post-irradiation. Application of a sunscreen containing ethylhexyl-p-methoxycinnamate or chemopreventive agent green tea polyphenols or silymarin to the skin of the mice prior to UVB exposure was found to prevent the formation of pyrimidine dimers.
Chatterjee
M L
ML
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Agarwal
R
R
Mukhtar
H
H
D000818:Animals; D004247:DNA / Q000528:radiation effects*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D005260:Female; D006160:Guanosine Triphosphate / Q000494:pharmacology; D051379:Mice; D008812:Mice, Hairless; D010761:Phosphorus Radioisotopes; D011740:Pyrimidine Dimers; D012838:Silymarin / Q000494:pharmacology; D012878:Skin Neoplasms / Q000517:prevention & control; D013473:Sunscreening Agents / Q000494:pharmacology; D014466:Ultraviolet Rays
D010761:Phosphorus Radioisotopes; D011740:Pyrimidine Dimers; D012838:Silymarin; D013473:Sunscreening Agents; D006160:Guanosine Triphosphate; D004247:DNA