DNA damage after acute exposure of mice skin to physiological doses of UVB and UVA light

Svobodová, Alena Rajnochová; Galandáková, Adéla; Šianská, Jarmila; Dolezal, Dalibor; Lichnovská, Radka; Ulrichová, Jitka; Vostalová, Jitka

doi:10.1007/s00403-012-1212-x

Cited by 78 publications

(64 citation statements)

References 18 publications

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“…In contrast, several DNA damage responses previously demonstrated in SKH-1 skin following UVB irradiation (22,24) are not modulated by absence of epithelial cell-specific COX-2 ( Figure 4B and C). The bulk of the early events mediated by COX-2 in response to acute UVB radiation appear to be associated with intrinsic, epithelial cell-autonomous COX-2 expression/function; COX-2 expression in other cell types seems to play a minor (if any) role.…”

Section: Discussionmentioning

confidence: 45%

“…To determine the effect of UVB irradiation on skin hyperplasia in SKH-1 mice, and the role of cell-specific COX-2 expression on this response, we measured epidermal thickness following UV exposure of SKH- Like γH2AX, p53 is an early response to a single UVB irradiation of SKH-1 mice (22)(23)(24). Sulindac, a cyclooxygenase inhibitor, is reported to reduce p53 expression in UVB-irradiated skin of SKH-1 mice (25 Figure 4C).…”

Section: Uvb-induced Skin Epidermal Hyperplasia Is Reduced Inmentioning

confidence: 99%

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Cell-type-specific roles for COX-2 in UVB-induced skin cancer

et al. 2014

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In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/ burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox ;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox ;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox ; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer.

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Section: Discussionmentioning

confidence: 45%

Section: Uvb-induced Skin Epidermal Hyperplasia Is Reduced Inmentioning

confidence: 99%

Cell-type-specific roles for COX-2 in UVB-induced skin cancer

et al. 2014

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“…In contrast, UVA-caused IL-10 accumulation is not linked to leukocyte infiltration (Fig. 3B) or DNA damage 28 , and may be connected to UVA-stimulated overproduction of reactive oxygen species and the following oxidant/antioxidant imbalance.…”

Section: Discussionmentioning

confidence: 90%

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Vostalová¹,

Svobodová²,

Galandáková³

et al. 2013

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Solar light generates inflammatory responses in exposed skin. These effects are generally attributed to UVB light. However, skin is exposed to a huge quantum of UVA photons as UVA is a predominant part of sunlight and the radiation used in tanning beds. We examined the effects of a single exposure to UVA and UVB wavebands on cytokine levels in skin and plasma, myeloperoxidase (MPO) activity, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in skin. Methods. Hairless mice were irradiated with either UVA (10 or 20 J/cm 2 ) or UVB (200 or 800 mJ/cm 2 ). The effects were assessed after 4/24 h. Plasma cytokine levels were evaluated using a Bio-Plex cytokine assay. Cytokine, iNOS and COX-2 levels in skin were determined by Western blot. Skin MPO activity was monitored spectrophotometrically. Results. UVB induced up-regulation of interleukin-1β (IL-1β) and interleukin-6 (IL-6) and decrease in interleukin-10 (IL-10) mainly after 4 h. In contrast, UVA caused increase in levels of tumor necrosis factor-alpha (TNF-α) and IL-6 after 4 h and up-regulated IL-10 and interleukin-12 (IL-12) after 24 h. The increase in MPO activity from infiltrated leucocytes was observed only in UVB irradiated animals. iNOS was up-regulated 4 h after UVA and UVB treatment. No significant effect on COX-2 expression was detected. Conclusions. UVA and UVB light affected several inflammatory markers. For individual waveband, changes in plasma parameters did not correlate with those in skin. Thus evaluation of plasma samples cannot simply be replaced by determination in skin specimens and vice versa.

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“…Unlike the shorter-wavelength UVB photons, which are almost completely absorbed by the epidermis, the longerwave length UVA photons can reach deeper dermal layer of skin and its blood vessels. Thus, the peripheral blood cells, including lymphocytes, can be exposed to UVA light even under physiological conditions 13 . The UVA radiation (0.1 J/cm 2 ) can produce around 80-130 DNA lesions per cell (human lymhocytes) that are detectable by the Comet assay 14 .…”

Section: Introductionmentioning

confidence: 99%

Genotoxic changes in peripheral lymphocytes after therapeutic exposure to crude coal tar and ultraviolet radiation

Málková¹,

Köhlerová²,

Fiala³

et al. 2016

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims. Goeckerman therapy is based on combined exposure to UV radiation (UVA, UVB) and crude coal tar (PAHs). Some indicators suggest a genotoxic hazard, however, the level of genotoxic risk of the therapy has not yet been investigated sufficiently. This study aims to assesss the genotoxic risk. Methods. The studied group consisted of patients with chronic stable plaque psoriasis treated by Goeckerman therapy (n = 29). Heparin-treated peripheral blood samples were collected one day before the first treatment and immediately after the last procedure. The lymphocytes were isolated from the blood. The level of genotoxicity was evaluated using an alkaline version of the Comet assay which detects DNA single strand breaks (DNA-SSBs), a neutral version of the Comet assay which detects DNA double strand breaks (DNA-DSBs), and using chromosomal aberrations. Results. The level of DNA-SSBs increased insignificantly (median; Q1-Q3): 1.4 (0.4; 0.1-1.4) vs. 2.5 (0.6; 0.3-2.7) %tDNA (P = 0.11) and the level of DNA-DSBs increased significantly: 7.8 (6.5; 3. 4-10.5) vs. 20.7 (19.3; 14.2-24.6) % DNA (P < 0.001). The total number of aberrated cells (P < 0.001) and structurally aberrated cells (P < 0.001) increased significantly. Conclusion. The elevated levels of the DNA-DSBs and the chromosomal aberrations in the peripheral lymphocytes indicated a genotoxic hazard. However, the elevated level of the chromosomal abnormalities was below the upper level of the reference range for healthy Czech adults. While, the genotoxic risk appears to be low, Goeckerman treatment represents a further contribution to the lifetime load of genotoxic factors.

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DNA damage after acute exposure of mice skin to physiological doses of UVB and UVA light

Cited by 78 publications

References 18 publications

Cell-type-specific roles for COX-2 in UVB-induced skin cancer

Cell-type-specific roles for COX-2 in UVB-induced skin cancer

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Genotoxic changes in peripheral lymphocytes after therapeutic exposure to crude coal tar and ultraviolet radiation

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