Topical DNA oligonucleotide therapy reduces UV-induced mutations and photocarcinogenesis in hairless mice

Goukassian, David A.; Helms, Elizabeth; Steeg, Harry van; Oostrom, Conny van; Bhawan, Jag; Gilchrest, Barbara A.

doi:10.1073/pnas.0306389101

Cited by 74 publications

(82 citation statements)

References 38 publications

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“…24 Sham-irradiated mice had only a background level of mutations (24 Ϯ 0 ϫ 10 Ϫ5 ) as reported previously for this assay. 19,25 And this level increased nearly fivefold (121.5 Ϯ 10 ϫ 10 Ϫ5 ) after a single UV exposure ( Figure 7). Compared with vehicle control, UVinduced mutations in PL-fed-mice were decreased by ϳ25% (121.5 Ϯ 10.05 ϫ 10 Ϫ5 vs. 90.9 Ϯ 10.6 ϫ 10 Ϫ5 , vehicle vs. PL, P Ͻ 0.058) when assessed 2 weeks after the single UV exposure (Figure 7).…”

Section: Polypodium Leucotomos Reduces Mutations In Murine Skin Aftermentioning

confidence: 99%

“…19 Twenty-five male mice, ages 2 to 3 months, were used in each group. Polypodium Leucotomos (PL) extract was provided by Industrial Farmacé utica Cantabria (Madrid, Spain) as a slightly sweet but otherwise tasteless powder and was given to mice fresh every day with drinking water.…”

Section: Animal Modelmentioning

confidence: 99%

“…19 Genomic DNA was isolated by using commercially available kit (Qiagen, Valencia, CA). We isolated 30 to 40 g of genomic DNA from each of the approximately 1 ϫ 2-cm tissue samples, which is enough to perform mutation analyses of the integrated lacZ gene as originally described by Boerrigter et al 21 The following paragraph is a brief overview of transgenic mouse model for mutagenesis studies based on analysis of mutations in lacZ/pUR288 plasmid incorporated in the mouse genome.…”

Section: Mutation Analysismentioning

confidence: 99%

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Polypodium leucotomos Extract Decreases UV-Induced Cox-2 Expression and Inflammation, Enhances DNA Repair, and Decreases Mutagenesis in Hairless Mice

Zattra

Coleman

Arad

et al. 2009

The American Journal of Pathology

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mice were fed for 10 days with PL (300 mg/kg) or vehicle then UV-irradiated, once. By 24 hours, UVinduced Cox-2 levels were increased in vehicle-fed and PL-fed mice, whereas by 48 and 72 hours, Cox-2 levels were four-to fivefold lower in PL-fed mice (P < 0.05). p53 expression/activity was increased in PL-fed versus vehicle-fed then UV-irradiated mice. UV-induced inflammation was decreased in PL-fed mice, as shown by ϳ60% decrease (P < 0.001) in neutrophil infiltration at 24 hours, and macrophages by ϳ50% (<0.02) at 24 and 48 hours. By 72 hours, 54 ؎ 5% cyclobutane pyrimidine dimers remained in vehiclefed versus 31 ؎ 5% in PL-fed skin (P < 0.003). The number of 8-hydroxy-2-deoxyguanosine-positive cells were decreased before UV irradiation by ϳ36% (P < 0.01), suggesting that PL reduces constitutive oxidative DNA damage. By 6 and 24 hours, the number of 8-hydroxy-2-deoxyguanosine-positive cells were ϳ59% (P < 0.01) and ϳ79% (P < 0.03) lower in PL-fed versus vehicle-fed mice. Finally, UV-induced mutations in PL-fed-mice were decreased by ϳ25% when assessed 2 weeks after the single UV exposure. These data demonstrate that PL extract supplementation affords the following photoprotective effects: p53 activation and reduction of acute inflammation via Cox-2 enzyme inhibition, increased cyclobutane pyrimidine dimer removal, and reduction of oxidative DNA damage.

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Section: Polypodium Leucotomos Reduces Mutations In Murine Skin Aftermentioning

confidence: 99%

Section: Animal Modelmentioning

confidence: 99%

Section: Mutation Analysismentioning

confidence: 99%

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Polypodium leucotomos Extract Decreases UV-Induced Cox-2 Expression and Inflammation, Enhances DNA Repair, and Decreases Mutagenesis in Hairless Mice

Zattra

Coleman

Arad

et al. 2009

The American Journal of Pathology

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“…However, Eller et al (15) first demonstrated that administration of DNA oligonucleotides induces DNA repair via a p53-dependent mechanism. Accordingly, a recent in vivo study indicated that topical pretreatment with DNA oligonucleotides enhanced the rate of DNA photoproduct removal, decreased UVinduced mutations, and reduced photocarcinogenesis in UV-irradiated mice (16). We recently observed that the immunostimulatory cytokine IL-12 is able to reduce the amount of DNA damage both in vitro and in vivo (17).…”

Section: Il-18mentioning

confidence: 99%

IL-18 Reduces Ultraviolet Radiation-Induced DNA Damage and Thereby Affects Photoimmunosuppression

Schwarz

Maeda

Ständer

et al. 2006

The Journal of Immunology

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UV-induced DNA damage has been recognized as the major molecular trigger for photoimmunosuppression. IL-12 prevents UV-induced immunosuppression via its recently discovered capacity to reduce DNA damage presumably via induction of DNA repair. Because IL-18 shares some biological activities with IL-12 we studied the effect of IL-18 on UV-induced DNA damage and immunosuppression. IL-18 reduced UV-induced apoptosis of keratinocytes and supported long-term cell survival on UV exposure. Injection of IL-18 into mice that were exposed to UV radiation significantly lowered the number of apoptotic keratinocytes. Accordingly, radiation immunohistochemistry revealed reduced amounts of DNA damage in epidermal cells upon injection of IL-18. These effects were not observed in DNA repair-deficient (XpaKO) mice, indicating that IL-18 like IL-12 reduces DNA damage via DNA repair. UV-mediated suppression of the induction of contact hypersensitivity, which is known to be primarily triggered by DNA damage, was prevented upon injection of IL-18 before UV exposure in wild-type but not in XpaKO mice. In contrast to IL-12, IL-18 was not able either in wild-type or in XpaKO mice to break UV-induced immunotolerance that is mediated via regulatory T cells rather than in a DNA damage-dependent fashion. This result indicates that IL-12 is still unique in its capacity to restore immune responses because of its effect on regulatory T cells. Together, these data identify IL-18 as a further cytokine that exhibits the capacity to affect DNA repair. Though being primarily a proinflammatory cytokine through this capacity, IL-18 can also foster an immune response that is suppressed by UV radiation.

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“…* T4 endonuclease: Assayed in patients with xerodermapigmentosum [36,37]. * DNA oligonucleotides: Enhance the cellular response to subsequent UV irradiation,regardless of the existence of previous DNA damage [38].…”

Section: Antioxidantsmentioning

confidence: 99%

Sunscreens and Antioxidants as Photo-protective Measures: An update

Hassan¹,

Dorjay²,

Sami³

et al. 2013

Our Dermatol Online

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There are many photo-protective measures adopted for protection from the solar radiation especially the UV radiation spectrum, sunscreens being the main agents. Besides the traditional approach of topical use of sunscreens, both chemical and physical, a new approach has emerged to use systemic agents in the form of vitamins and minerals. In this review, we are describing the major aspects related to sunscreens and anti-oxidants as photo-protective measures.

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Topical DNA oligonucleotide therapy reduces UV-induced mutations and photocarcinogenesis in hairless mice

Cited by 74 publications

References 38 publications

Polypodium leucotomos Extract Decreases UV-Induced Cox-2 Expression and Inflammation, Enhances DNA Repair, and Decreases Mutagenesis in Hairless Mice

Polypodium leucotomos Extract Decreases UV-Induced Cox-2 Expression and Inflammation, Enhances DNA Repair, and Decreases Mutagenesis in Hairless Mice

IL-18 Reduces Ultraviolet Radiation-Induced DNA Damage and Thereby Affects Photoimmunosuppression

Sunscreens and Antioxidants as Photo-protective Measures: An update

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