Demonstration of UV-dimers in human skin DNA in situ 3 weeks after exposure.
Data on DNA repair rates of specific types of DNA lesions are very limited in humans in situ. Rate of repair of UV-induced DNA damage was followed in the skin of 17 volunteers up to 3 weeks of UV exposure, using a (32)P-postlabelling technique for the determination of specific photoproducts. The subjects of skin phototypes I and IV were exposed to 40 mJ/cm(2) of solar simulating radiation on buttock skin, and biopsies were taken at 0 h, 48 h and 3 weeks of exposure for the analysis of two cyclobutane pyrimidine dimers, TT=C and TT=T, and two 6-4 photoproducts, TT-C and TT-T, as trinucleotides. Repair rates were heterogeneous for different photoproducts. T=T dimers were repaired slower than C=T dimers, and 2.3-9.0% of the initial T=T damage remained unrepaired after 3 weeks, and was detectable in 16/17 subjects. The identity of the identified photoproducts was confirmed by a photochemical reversion assay. Damage level correlated with skin types, type I being more sensitive than type IV in an age-matched comparison. This is the first time the persistence of defined human DNA damage is demonstrated up to 3 weeks. Long-lasting DNA damage increases the likelihood of mutations.
Hemminki
Kari
K
Department of Biosciences at Novum, Karolinska Institute, 14157 Huddinge, Sweden. kari.hemminki@cnt.ki.se
Xu
Guogang
G
Kause
Laura
L
Koulu
Leena M
LM
Zhao
Chunyan
C
Jansen
Christer T
CT
D000328:Adult; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D019281:Dimerization; D006801:Humans; D008027:Light; D009154:Mutation; D012867:Skin / Q000528:radiation effects*; D013941:Thymine / Q000737:chemistry; D013997:Time Factors; D014466:Ultraviolet Rays
D004247:DNA; D013941:Thymine