Urinary Thymidine Dimer as a Marker of Total Body Burden of UV-Inflicted DNA Damage in Humans

High levels of DNA damage are induced in human skin following exposure to UV radiation. Cyclobutane thymidine dimer (T = T) is the most common of these lesions, which are enzymatically removed as oligonucleotides from DNA and further degraded before excretion in urine. Analysis of such repair products in the urine could serve as a biomarker of total body burden of UV exposure. The aim of this study was to examine the kinetics of T = T excretion following a single tanning session in a commercial solarium and to validate the method by delivering different doses. Ten individuals used the solarium for a total of 35 sessions of body tanning. Urine was collected before UV exposure and daily thereafter (up to 5 or 11 days) and T = T was analyzed using a very sensitive and quantitative 32P-postlabeling technique combined with high-performance liquid chromatography. Following exposure, T = T levels increased dramatically and reached a peak 3 days later; afterwards, the T = T levels gradually decreased. The total amount of T = T excreted differed about 5-fold among subjects given an equal dose. A 50% excretion time was calculated using the excretion data for the first 5 days and it was found to be between 55 and 76 hours for different individuals. There was a good correlation between the amount of T = T excreted during days 1 to 5 and the delivered UV dose. Reducing exposure time to 50% lowered the amount of T = T to 47%; if half of the lamps were covered, T = T decreased to 44%. Our data show that urinary T = T could be a suitable noninvasive biomarker for UV exposure; a finding which could also be applicable to studies in children. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2868–72)

[1]  A. Sancar,et al.  Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. , 2004, Annual review of biochemistry.

[2]  K. Hemminki,et al.  Cyclobutane thymidine dimers are present in human urine following sun exposure: quantitation using 32P-postlabeling and high-performance liquid chromatography. , 2001, The Journal of investigative dermatology.

[3]  M. Evans,et al.  Induction and excretion of ultraviolet-induced 8-oxo-2'-deoxyguanosine and thymine dimers in vivo: implications for PUVA. , 2001, The Journal of investigative dermatology.

[4]  M. Evans,et al.  Urinary thymine dimers and 8‐oxo‐2′‐deoxyguanosine in psoriasis , 1999, FEBS letters.

[5]  B. Jansson,et al.  Population UV-dose and skin area--do sunbeds rival the sun? , 1999, Health physics.

[6]  Jacques Ferlay,et al.  Estimates of the worldwide incidence of 25 major cancers in 1990 , 1999, International journal of cancer.

[7]  K. Hemminki,et al.  In situ repair of cyclobutane pyrimidine dimers and 6-4 photoproducts in human skin exposed to solar simulating radiation. , 1999, The Journal of investigative dermatology.

[8]  K. Hemminki,et al.  Ultraviolet B-induced DNA damage in human skin and its modulation by a sunscreen. , 1998, Cancer research.

[9]  D. English,et al.  Sun exposure and Skin Cancer , 1997, The Australasian journal of dermatology.

[10]  R. Dawber,et al.  Treatment of lentigo maligna , 1997, The Australasian journal of dermatology.

[11]  K. Kraemer Sunlight and skin cancer: another link revealed. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[12]  W. Lambert,et al.  The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm. , 1994, Archives of dermatology.

[13]  M. Paterson,et al.  Enzymatic analysis of isomeric trithymidylates containing ultraviolet light-induced cyclobutane pyrimidine dimers. II. Phosphorylation by phage T4 polynucleotide kinase. , 1989, The Journal of biological chemistry.

[14]  B Seaton,et al.  Simplified manual high performance clinical chemistry methods for developing countries. , 1984, Medical laboratory sciences.

[15]  J. Ferlay,et al.  Globocan 2000 : cancer incidence, mortality and prevalence worldwide , 2001 .

[16]  K. Hemminki,et al.  Ultraviolet radiation-induced photoproducts in human skin DNA as biomarkers of damage and its repair. , 2001, IARC scientific publications.

[17]  J. Cadet DNA damage caused by oxidation, deamination, ultraviolet radiation and photoexcited psoralens. , 1994, IARC scientific publications.

[18]  H. Bartsch,et al.  IARC monographs on the evaluation of carcinogenic risks to humans. Solar and ultraviolet radiation. , 1992, IARC monographs on the evaluation of carcinogenic risks to humans.