Abstract:
:We hypothesized that a substantial portion of the mutagenic alterations produced in the basal layer of human skin by sunlight are induced by wavelengths in the UVA range. Using laser capture microdissection we examined separately basal and suprabasal keratinocytes from human skin squamous cell carcinomas and premalignant solar keratosis for both UVA- and UVB-induced adduct formation and signature mutations. We found that UVA fingerprint mutations were detectable in human skin squamous cell carcinomas and solar keratosis, mostly in the basal germinative layer, which contrasted with a predominantly suprabasal localization of UVB fingerprint mutations in these lesions. The epidermal layer bias was confirmed by immunohistochemical analyses with a superficial localization of cyclobutane thymine dimers contrasting with the localization of 8-hydroxy-2'-deoxyguanine adducts to the basal epithelial layers. If unrepaired, these adducts may lead to fixed genomic mutations. The basal location of UVA-rather than UVB-induced DNA damage suggests that longer-wavelength UVR is an important carcinogen in the stem cell compartment of the skin. Given the traditional emphasis on UVB, these results may have profound implications for future public health initiatives for skin cancer prevention.
journal_name
Proc Natl Acad Sci U S Aauthors
Agar NS,Halliday GM,Barnetson RS,Ananthaswamy HN,Wheeler M,Jones AMdoi
10.1073/pnas.0401141101keywords:
subject
Has Abstractpub_date
2004-04-06 00:00:00pages
4954-9issue
14eissn
0027-8424issn
1091-6490pii
0401141101journal_volume
101pub_type
杂志文章abstract::DNA sequences in Neurospora crassa that code for ribosomal RNA have been isolated in a highly purified state by DNA-RNA hybridization. About 100 separate ribosomal RNA genes exist in each nucleus. These genes are composed of repeated sequences that are present about 100 times per nucleus. The individual members of thi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.69.11.3256
更新日期:1972-11-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.1403667112
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0611686104
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2018-05-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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