Human Melanocytes and Keratinocytes Exposed to UVB or UVA In Vivo Show Comparable Levels of Thymine Dimers

Young, Antony R.; Potten, Christopher S; Nikaido, Osamu; Parsons, Peter G.; Boenders, Jack; Ramsden, J; Chadwick, Carolyn

doi:10.1046/j.1523-1747.1998.00435.x

Cited by 104 publications

(79 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results clearly demonstrate that CPDs also are produced in significant yield in the whole human skin exposed to UVA radiation, in agreement with data obtained by immunohistochemistry (25,47,48). CPDs were predominantly produced at TT sites after UVA irradiation of human skin.…”

Section: Discussionsupporting

confidence: 91%

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.

581

569

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 91%

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.

581

569

View full text Add to dashboard Cite

show abstract

“…We suggest that combining the results of the studies is appropriate, as there is no convincing human data demonstrating that UVB is more or less strongly related to melanoma than UVA. In fact, there is some evidence that melanocytes exposed in vivo to either UVA or to UVB show similar levels of thymine dimer formation (23). In addition, studies have shown that UVA as well as UVB impairs antioxidant function and promotes reactive oxygen species, events known to be involved in cutaneous carcinogenesis (24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Tanning Beds, Sunlamps, and Risk of Cutaneous Malignant Melanoma

Gallagher

Spinelli

Lee

2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

210

141

View full text Add to dashboard Cite

Background: A number of studies have been conducted evaluating the risk of cutaneous malignant melanoma after exposure to sunlamps and/or sunbeds. The proportion of subjects in the individual studies who have reported exposure has, in general, been modest, and the resulting risk estimates for melanoma have been unstable with wide 95% confidence intervals (95% CI). The inconclusive results seen in individual studies have resulted in confusion as to the carcinogenicity of these devices. Methods: We conducted a systematic review and metaanalysis of these studies. A review of the literature from Jan 1, 1984 to April 2004 using MEDLINE identified 12 casecontrol studies and 1 cohort study which quantitatively evaluated the use of sunlamps and/or sunbeds and subsequent melanoma. After applying exclusion/inclusion criteria, 9 case-control and 1 cohort study provided data for the analysis. Summary odds ratios (OR) and 95% CIs for sunlamp/

show abstract

“…In fact, UVA radiation has been shown since the 1970s, first in bacteria (29) and then in mammalian cells (32,55,(80)(81)(82)(83)(84) and human skin (61,65,(85)(86)(87), to be also able to induce CPDs. However, these observations have been poorly considered until recently.…”

Section: Uva-induced Cpdsmentioning

confidence: 99%

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions^†

Cadet¹,

Mouret²,

Ravanat³

et al. 2012

Photochem & Photobiology

267

251

View full text Add to dashboard Cite

The survey focuses on recent aspects of photochemical reactions to cellular DNA that are implicated through the predominant formation of mostly bipyrimidine photoproducts in deleterious effects of human exposure to sunlight. Recent developments in analytical methods have allowed accurate and quantitative measurements of the main DNA photoproducts in cells and human skin. Highly mutagenic CC and CT bipyrimidine photoproducts, including cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are generated in low yields with respect to TT and TC photoproducts. Another striking finding deals with the formation of Dewar valence isomers, the third class of bipyrimidine photoproducts that is accounted for by UVA-mediated isomerization of initially UVB generated 6-4PPs. Cyclobutadithymine (T< >T) has been unambiguously shown to be involved in the genotoxicity of UVA radiation. Thus, T< >T is formed in UVA-irradiated cellular DNA according to a direct excitation mechanism with a higher efficiency than oxidatively generated DNA damage that arises mostly through the Type II photosensitization mechanism. C<>C and C< >T are repaired at rates intermediate between those of T< >T and 6-4TT. Evidence has been also provided for the occurrence of photosensitized reactions mediated by exogenous agents that act either in an independent way or through photodynamic effects.

show abstract

Human Melanocytes and Keratinocytes Exposed to UVB or UVA In Vivo Show Comparable Levels of Thymine Dimers

Cited by 104 publications

References 22 publications

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

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

Tanning Beds, Sunlamps, and Risk of Cutaneous Malignant Melanoma

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions^†

Contact Info

Product

Resources

About

Human Melanocytes and Keratinocytes Exposed to UVB or UVA In Vivo Show Comparable Levels of Thymine Dimers

Cited by 104 publications

References 22 publications

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

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

Tanning Beds, Sunlamps, and Risk of Cutaneous Malignant Melanoma

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions†

Contact Info

Product

Resources

About

Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions^†