DNA Photoproducts (dna + photoproduct)

Distribution by Scientific Domains

Selected Abstracts

Mechanisms of mutation formation with long-wave ultraviolet light (UVA)

Thomas M. Rünger
Summary Long-wave ultraviolet (UV) A light is able to damage DNA, to cause mutations, and to induce skin cancer, but the exact mechanisms of UVA-induced mutation formation remain a matter of debate. While pyrimidine dimers are well established to mediate mutation formation with shortwave UVB, other types of DNA damage, such as oxidative base damage, have long been thought to be the premutagenic lesions for UVA mutagenesis. However, pyrimidine dimers can also be generated by UVA, and there are several lines of evidence that these are the most important premutagenic lesions not only for UVB- but also for UVA-induced mutation formation. C,T transition mutations, which are generated by pyrimidine dimers, are called UV-signature mutations. They cannot be interpreted to be solely UVB-induced, as they are induced by UVA as well. Furthermore, there is no consistent evidence for a separate UVA-signature mutation that is only generated with UVA. We hypothesize that a weaker anti-mutagenic cellular response, but not a different type of DNA damage, may be responsible for a higher mutation rate per DNA photoproduct with UVA, as compared with UVB. [source]

Accumulation of DNA damage in Antarctic mosses: correlations with ultraviolet-B radiation, temperature and turf water content vary among species

Abstract The susceptibility of three East Antarctic moss species to UV-B radiation was examined by measuring accumulation of cyclobutane pyrimidine dimers under natural sunlight during the austral summer season of 2002/03. The 2002/03 season was characterized by unusually low springtime ozone depletion and as such our results likely underestimate the DNA damage possible in a more typical UV-B radiation season. Despite this all three species accumulated significant DNA photoproducts. We also found a positive association between photoproduct accumulation and incident UV-B radiation in the two cosmopolitan species, Bryum pseudotriquetrum and Ceratodon purpureus, with more DNA damage in samples collected early in the season compared with later in the summer. For B. pseudotriquetrum, negative associations were also observed between photoproduct accumulation and both turf water content and the 10-day mean air temperature. Photoproduct accumulation in the endemic species Schistidium antarctici was similarly high across the season and no significant association with environmental variables was found. Our results are consistent with the two cosmopolitan species having somewhat higher UV-B-screening capabilities and possibly more efficient mechanisms for repairing DNA damage than the endemic S. antarctici. [source]

Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation

David Mitchell
Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6,4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirwayÔ) and human skin (EpiDermÔ) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. [source]

Fluorometric Analysis of DNA Unwinding (FADU) as a Method for Detecting Repair-induced DNA Strand Breaks in UV-irradiated Mammalian Cells,

Christa Baumstark-Khan
ABSTRACT Fluorometric analysis of DNA unwinding (FADU assay) was originally designed to detect X-ray,induced DNA damage in repair-proficient and repair-deficient mammalian cell lines. The method was modified and applied to detect DNA strand breaks in Chinese hamster ovary (CHO) cells exposed to ionizing radiation as well as to UV light. Exposed cells were allowed to repair damaged DNA by incubation for up to 1 h after exposure under standard growth conditions in the presence and in the absence of the DNA synthesis inhibitor aphidicolin. Thereafter, cell lysates were mixed with 0.15 M sodium hydroxide, and DNA unwinding took place at pH 12.1 for 30 min at 20°C. The amount of DNA remaining double-stranded after alkaline reaction was detected by binding to the Hoechst 33258 dye (bisbenzimide) and measuring the fluorescence. After exposure to X-rays DNA strand breaks were observed in all cell lines immediately after exposure with subsequent restitution of high molecular weight DNA during postexposure incubation. In contrast, after UV exposure delayed production of DNA strand break was observed only in cell lines proficient for nucleotide excision repair of DNA photoproducts. Here strand break production was enhanced when the polymerization step was inhibited by adding the repair inhibitor aphidicolin during repair incubation. These results demonstrate that the FADU approach is suitable to distinguish between different DNA lesions (strand breaks versus base alterations) preferentially induced by different environmental radiations (X-rays versus UV) and to distinguish between the different biochemical processes during damage repair (incision versus polymerization and ligation). [source]