Cited by 156DNA Repair MechanismsCarcinogens and Genotoxicity AssessmentSkin Protection and Aging

DNA lesions induced by UV A1 and B radiation in human cells: Comparative analyses in the overall genome and in the p53 tumor suppressor gene

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Besaratinia, Ahmad, Synold, Timothy W., Chen, Hsiu-Hua, Chang, Cheng, Xi, Bixin, Riggs, Arthur D., Pfeifer, Gerd P.·2005·Proceedings of the National Academy of Sciences

Abstract

The UV components of sunlight (UVA and UVB) are implicated in the etiology of human skin cancer. The underlying mechanism of action for UVB carcinogenicity is well defined; however, the mechanistic involvement of UVA in carcinogenesis is not fully delineated. We investigated the genotoxicity of UVA1 versus UVB in the overall genome and in the p53 tumor suppressor gene in normal human skin fibroblasts. Immuno-dot blot analysis identified the cis - syn cyclobutane pyrimidine-dimer (CPD) as a distinctive UVB-induced lesion and confirmed its formation in the genomic DNA of UVA1-irradiated cells dependent on radiation dose. HPLC/tandem MS analysis showed an induction of 8-oxo-7,8-dihydro-2′-deoxyguanosine in the genomic DNA of UVA1-irradiated cells only. Mapping of DNA damages by terminal transferase-dependent PCR revealed preferential, but not identical, formation of polymerase-blocking lesions and/or strand breaks along exons 5-8 of the p53 gene in UVB- and UVA1-irradiated cells. The UVB-induced lesions detected by terminal transferase-PCR were almost exclusively mapped to pyrimidine-rich sequences; however, the UVA1-induced lesions were mapped to purine- and pyrimidine-containing sequences along the p53 gene. Cleavage assays with lesion-specific DNA repair enzymes coupled to ligation-mediated PCR showed preferential, but not identical, formation of CPDs along the p53 gene in UVB- and UVA1-irradiated cells. Additionally, dose-dependent formation of oxidized and ring-opened purines and abasic sites was established in the p53 gene in only UVA1-irradiated cells. We conclude that UVA1 induces promutagenic CPDs and oxidative DNA damage at both the genomic and nucleotide resolution level in normal human skin fibroblasts.

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  • UVA radiation has been shown since the 1970s to induce CPDs in bacteria, mammalian cells and human skin.

    “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.”

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Authors
Besaratinia, A., Synold, T. W., Chen, H.-H., Chang, C., Xi, B., Riggs, A. D., & Pfeifer, G. P.
Affiliations
  • Division of Biology, Beckman Research Institute, and Department of Medical Oncology, The City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010; and Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan
  • City Of Hope National Medical Center (US)
Venue
Proceedings of the National Academy of Sciences
Published
2005-07-11
Volume
102
Issue
29
Pages
10058-10063
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2150956753
Cited by
156
References
64
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 8 · 2016: 15 · 2015: 3 · 2014: 7 · 2013: 11 · 2012: 8
FWCI
4.66
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Environmental Health Sciences (R37ES006070, R01ES006070, ES-06070)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Keywords
UV-B radiation, DNA damage, p53 gene, cyclobutane pyrimidine dimers, 8-oxo-7,8-dihydro-2'-deoxyguanosine, oxidative DNA damage, abasic sites, dermal fibroblasts, skin cancer, DNA repair enzymes, strand breaks, genotoxicity
MeSH terms
Cells, Cultured, Chromatography, High Pressure Liquid, DNA Damage, Dose-Response Relationship, Radiation, Humans, Pyrimidine Dimers, Mass Spectrometry, Ultraviolet Rays, Immunoblotting, Genome, Human, Polymerase Chain Reaction, Genes, p53, DNA Repair Enzymes

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