DNA damage in UVB-irradiated keratinocytes

Maccubbin, Alexander E.; Przybyszewski, Joseph; Evans, Marianne S.; Budzinski, Edwin E.; Patrzyc, Helen B.; Kulesz‐Martin, Molly; Box, Harold C.

doi:10.1093/carcin/16.7.1659

Cited by 21 publications

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“…(42)(43)(44) However, those techniques had a limitation derived from the artifactual oxidation of DNA during its extraction. It was recently reported that relatively low doses of UVB (62.5-500 mJ/cm 2 ) cause dose-dependent increases in 8-OH-dG, and DNA from unirradiated normal human epidermal keratinocytes contains 1.49 ± 0.11 8-OH-dG residues per 10 6 dG.…”

Section: Discussionmentioning

confidence: 99%

Formation of 8‐hydroxy‐2′‐deoxyguanosine in the DNA of cultured human keratinocytes by clinically used doses of narrowband and broadband ultraviolet B and psoralen plus ultraviolet A

et al. 2006

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Psoralen plus ultraviolet A (PUVA) and narrowband ultraviolet B (UVB) are widely used in skin disease phototherapy. Recently, the efficacy of UVB therapy has been greatly improved by narrowband UVB, compared to conventional broadband UVB. The objectives of the current study were to evaluate the influence of UVB-induced and PUVA-induced oxidative stress on cultured keratinocytes. We analyzed 8-hydroxy-2′ ′ ′ ′-deoxyguanosine (8-OH-dG) in human keratinocytes (HaCaT cell line) using a highperformance liquid chromatography system equipped with an electrochemical detector. Non-irradiated human keratinocytes contained a baseline of 1.48 ± ± ± ± 0.22 (mean ± ± ± ± SD) 8-OH-dG per 10 6 deoxyguanosine (dG) residues in cellular DNA, which increased linearly with higher doses of UVB. When their abilities to induce 8-OH-dG were compared to each other, based on the minimal erythemal and therapeutically used doses, by irradiating them with broadband UVB at 100 mJ/cm 2 , the amount of 8-OH-dG increased to 3.42 ± ± ± ± 0.46 residues per 10 6 dG, while a narrowband UVB treatment at 1000 mJ/cm 2 , with biological effects comparable to those elicited by 100 mJ/cm 2 broadband UVB, increased it to 2.06 ± ± ± ± 0.31 residues per 10 6 dG. PUVA treatment, with 100 ng/mL 8-methoxypsoralen and 5000 mJ/cm 2 UVA, increased the 8-OH-dG level to 4.52 ± ± ± ± 0.42 residues per 10 6 dG. When HaCaT cells treated with 2000 mJ/cm 2 narrowband UVB were cultured and the amount of 8-OH-dG was monitored in the living cells, 65.6% of the residues were repaired 24 h after treatment. Our study provides a warning that widely used narrowband UVB and PUVA induce cellular oxidative DNA damage at the therapeutically used doses, although to a lesser degree than broadband UVB with the same clinically effective dose. (Cancer Sci 2006; 97: 99 -105) E ight-hydroxy-2′-deoxyguanosine (8-OH-dG), also known as 7,8-dihydro-8-oxo-deoxyguanosine (8-oxo-dG), (1) has been proposed as a key biomarker of oxidative DNA damage relevant to carcinogenesis (1,2) and pathogenesis of autoimmune disorders. (3,4) This DNA damage is induced by the reactions of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ), superoxide anions ( ), singlet oxygen and hydroxyl radicals (·OH).Human skin is constantly exposed to environmental stresses, and is vulnerable to the effects of ROS generated by exposure to ultraviolet (UV) radiation.(5) Yamamoto et al. (6) reported that the formation of 8-OH-dG in DNA might be one of the mechanisms of daylight-induced mutagenesis. In fact, irradiation with a fluorescent sun lamp or with UVB does induce 8-OH-dG in the epidermis of hairless mice. (7,8) Parrish and Jaenicke (9) found that 313 nm UVB radiation is the most effective wavelength for the treatment of psoriasis. This finding provided the impetus for developing the Philips TL-01 fluorescent bulb, a narrowband UVB light source that produces a spectral emission between 310 and 315 nm. Narrowband UVB phototherapy has thus significantly improved the therapeutic efficacy of conventional br...

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Section: Discussionmentioning

confidence: 99%

Formation of 8‐hydroxy‐2′‐deoxyguanosine in the DNA of cultured human keratinocytes by clinically used doses of narrowband and broadband ultraviolet B and psoralen plus ultraviolet A

et al. 2006

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Section: Dna Damagementioning

confidence: 99%

“…57 These UV-B signature molecules have been demonstrated in keratinocytes and Langerhans cells on UV-B radiation. 57 CPD were shown to be involved in UV-B-induced apoptosis, inflammation, immunosuppression, and photocarcinogenesis. 58 Interestingly, UVinduced tumor formation could be prevented by repair of CPD in the basal keratinocytes only, but this was not the case for UV-induced immunosuppression, demonstrating that different cell types mediate different biologic effects of UV radiation.…”

Section: Dna Damagementioning

confidence: 99%

Phototherapy and Photochemotherapy for Psoriasis

Racz,

Prens

2015

Dermatologic Clinics

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“…Sunburn erythema may represent another condition where PARP activation may occur. Ultraviolet B radiation itself causes DNA breakage (126), which may trigger PARP activation. Moreover, as discussed earlier, peroxynitrite is produced in UVB irradiated skin, and an peroxynitrite‐induced DNA breakage may also cause PARP activation.…”

Section: Activation Of Poly(adp‐ribose) Polymerase By Peroxynitrite: mentioning

confidence: 99%

Nitric oxide‐peroxynitrite‐poly(ADP‐ribose) polymerase pathway in the skin

Virág

Szabó

Bakondi³

et al. 2002

Experimental Dermatology

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In the last decade it has become well established that in the 2 Dermatology, Faculty of Medicine, University of skin, nitric oxide (NO), a diffusable gas, mediates various physiologic Debrecen, Debrecen, Hungary, and 3 Inotek Inc., Beverly, MA, USA functions ranging from the regulation of cutaneous blood flow to melanogenesis. If produced in excess, NO combines with superoxide anion to form peroxynitrite (ONOO -), a cytotoxic oxidant that has been made responsible for tissue injury during shock, inflammation and ischemia-reperfusion. The opposite effects of NO and ONOO -on various cellular processes may explain the 'double-edged sword' nature of NO depending on whether or not cellular conditions favour peroxynitrite formation. Peroxynitrite has been shown to activate the nuclear nick sensor enzyme, poly(ADP-ribose) polymerase (PARP). Overactivation of PARP depletes the cellular stores of NAD π , the substrate of PARP, and the ensuing 'cellular energetic catastrophy' results in necrotic cell death. Whereas the role of NO in numerous skin diseases including wound healing, burn injury, psoriasis, irritant and allergic contact dermatitis, ultraviolet (UV) light-induced sunburn erythema and the control of skin infections has been extensively documented, the intracutaneous role of Key words: inflammation -keratinocyte -nitric peroxynitrite and PARP has not been fully explored. We have recently oxide -peroxynitrite -poly(ADP-ribose) polymerase -skin demonstrated peroxynitrite production, DNA breakage and PARP activation in a murine model of contact hypersensitivity, and propose that

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DNA damage in UVB-irradiated keratinocytes

Cited by 21 publications

References 0 publications

Formation of 8‐hydroxy‐2′‐deoxyguanosine in the DNA of cultured human keratinocytes by clinically used doses of narrowband and broadband ultraviolet B and psoralen plus ultraviolet A

Formation of 8‐hydroxy‐2′‐deoxyguanosine in the DNA of cultured human keratinocytes by clinically used doses of narrowband and broadband ultraviolet B and psoralen plus ultraviolet A

Phototherapy and Photochemotherapy for Psoriasis

Nitric oxide‐peroxynitrite‐poly(ADP‐ribose) polymerase pathway in the skin

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