In Situ Repair of Cyclobutane Pyrimidine Dimers and 6–4 Photoproducts in Human Skin Exposed to Solar Simulating Radiation

Bykov, Vladimir J.N.; Sheehan, John M.; Hemminki, Kari; Young, Antony R.

doi:10.1046/j.1523-1747.1999.00523.x

Cited by 97 publications

(87 citation statements)

References 46 publications

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“…This normalization did not change the ranges or the relative SDs of the data, demonstrating that other factors are more important for determining interindividual differences in urinary excretion of T = T. There was no correlation between skin type or age and total amount of T = T. This was maybe not unexpected because only skin types II and III were represented, and the population was small in size and similar in age, making it difficult to detect possible differences. In studies of T = T levels in human skin in situ, similar or even larger interindividual differences were noted (14,17). The doses used in the latter studies were erythema-weighted and the observed interindividual variations could therefore not be explained by differences in skin types.…”

Section: Discussionmentioning

confidence: 75%

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

Kotova

Hemminki²,

Segerbäck

2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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 32 P-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)

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Section: Discussionmentioning

confidence: 75%

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

Kotova

Hemminki²,

Segerbäck

2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…These works led to the conclusion that TϽϾC was the major lesion generated (38)(39)(40). However, it may be pointed out that the same approach failed to provide reproducible data concerning the formation of CPDs in skin exposed to simulated sunlight (36,37,(41)(42)(43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation

Mouret

Baudouin

Charvéron

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

585

569

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Solar UV radiation is the most important environmental factor involved in the pathogenesis of skin cancers. The well known genotoxic properties of UVB radiation (290 -320 nm) mostly involve bipyrimidine DNA photoproducts. In contrast, the contribution of more-abundant UVA radiation (320 -400 nm) that are not directly absorbed by DNA remains poorly understood in skin. Using a highly accurate and quantitative assay based on HPLC coupled with tandem mass spectrometry, we determined the type and the yield of formation of DNA damage in whole human skin exposed to UVB or UVA. Cyclobutane pyrimidine dimers, a typical UVBinduced DNA damage, were found to be produced in significant yield also in whole human skin exposed to UVA through a mechanism different from that triggered by UVB. Moreover, the latter class of photoproducts is produced in a larger amount than 8-oxo-7,8-dihydro-2-deoxyguanosine, the most common oxidatively generated lesion, in human skin. Strikingly, the rate of removal of UVA-generated cyclobutane pyrimidine dimers was lower than those produced by UVB irradiation of skin. Finally, we compared the formation yields of DNA damage in whole skin with those determined in primary cultures of keratinocytes isolated from the same donors. We thus showed that human skin efficiently protects against UVB-induced DNA lesions, whereas very weak protection is afforded against UVA. These observations emphasize the likely role played by the UVA-induced DNA damage in skin carcinogenesis and should have consequences for photoprotection strategies.carcinogenesis ͉ DNA damage ͉ mutagenesis ͉ oxidative stress ͉ DNA repair O ccurrence of skin cancers, which mostly arise from exposure to solar UV radiation, has constantly increased in the recent years due to changes in life habits. Harmful effects of UV radiation are mostly associated with both direct and indirect photoinduced damage to DNA (1) that can lead to the induction of mutations. The chemical nature and the formation efficiency of the DNA lesions greatly depend on the wavelength of the incident photons. UVB radiation (290-320 nm), the most energetic mutagenic and carcinogenic component of solar radiation, is directly absorbed by DNA, giving rise to dimeric photoproducts between adjacent pyrimidine bases. Two types of these bulky modifications are produced, namely cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (1). Evidence for the involvement of these lesions in photocarcinogenesis is provided by the high proportion of p53 mutations (TC to TT or CC to TT transitions) detected at bipyrimidine sites in skin tumors (2-4).UVA radiation (320-400 nm), the other component of terrestrial UV radiation, is mutagenic in cultured cells (5, 6) and induces skin tumors in mice (7,8). In addition, UVA has been shown to be involved in immunosuppression (9) and is suspected to play a major role in the induction of melanoma (10, 11), the most severe type of skin cancers. Consequently, the carcinogenic properties of UVA have become a matter of concern...

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“…Because humans vary up to 10-fold in their individual DNA repair capacity of distinct cell types as shown (e.g., for blood lymphocytes) (Buschfort-Papewalis et al, 2002), skin fibroblasts (Bykov et al, 1999), or gut epithelium cells (Lees et al, 2006), such variations in the target cells of cisplatin neurotoxicity may account for the interindividual differences in latency and severity of PNP symptoms. Previous postmortem measurements of augmented tissue platinum content in patients with clinical signs of neuropathy further support this assumption (Gregg et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Repair Capacity for Platinum-DNA Adducts Determines the Severity of Cisplatin-Induced Peripheral Neuropathy

Dzagnidze¹,

Katsarava²,

Makhalova³

et al. 2007

J. Neurosci.

141

116

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The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine-guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific monoclonal antibodies.

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In Situ Repair of Cyclobutane Pyrimidine Dimers and 6–4 Photoproducts in Human Skin Exposed to Solar Simulating Radiation

Cited by 97 publications

References 46 publications

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

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

Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation

Repair Capacity for Platinum-DNA Adducts Determines the Severity of Cisplatin-Induced Peripheral Neuropathy

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