Demonstration of UV-dimers in human skin DNA in situ 3 weeks after exposure

• Published in: Carcinogenesis (New York) Vol. 23; no. 4; pp. 605 - 609
• Main Authors: Hemminki, Kari, Xu, Guogang, Kause, Laura, Koulu, Leena M., Zhao, Chunyan, Jansen, Christer T.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2002; Oxford Publishing Limited (England)
• Subjects: Adult; Biological and medical sciences; Biological effects of radiation; CPD; cyclobutane dimers; cyclobutane pyrimidine dimers; Dimerization; DNA - radiation effects; DNA Damage; DNA Repair; Fundamental and applied biological sciences. Psychology; Humans; Light; MED; minimal erythemal dose; Mutation; NER; Non ionizing radiations. Hertzian waves. Biooptics; nucleotide excision repair; Skin - radiation effects; solar simulating radiation; SSR; Thymine - chemistry; Time Factors; Tissues, organs and organisms biophysics; TT=C and TT=T; Ultraviolet Rays; Human; Ultraviolet radiation; Healthy subject; Toxicity; DNA; In situ; Volunteer; Time interval; Skin; Biological effect; Lesion; Pyrimidine dimer
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/23.4.605

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 32P-postlabelling technique for the determination of specific photoproducts. The subjects of skin phototypes I and IV were exposed to 40 mJ/cm2 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.