The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm

Kraemer, Kenneth H.

doi:10.1001/archderm.130.8.1018

Cited by 251 publications

(251 citation statements)

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“…The importance and efficacy of the NER is best illustrated by the disease xeroderma pigmentosum (XP). Due to genetic mutations in the various NER genes, XP patients do not exhibit a functional NER and suffer from a dramatically increased risk of developing UV-induced skin cancer at an early age (11). Accordingly, mice in which the different genes of the NER complex have been knocked out (KO) develop skin tumors upon chronic UV exposure earlier and at higher frequency when compared with wild-type (WT) mice (12).…”

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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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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“…XP patients are classified into specific complementation groups (XP-A through XP-G) depending on which XP gene is abnormal. Patients with XP experience 1000-fold higher incidences of basal and squamous cell carcinomas and malignant melanomas of the skin and more rarely, especially for XP-C patients, neurological symptoms (18)(19)(20). Different sensitivities to UV radiation and different susceptibilities to tumor development are observed among the XP complementation groups (21).…”

mentioning

confidence: 99%

Biochemical and Structural Domain Analysis of Xeroderma Pigmentosum Complementation Group C Protein

et al. 2006

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“…Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by hypersensitivity to sunlight, abnormal pigmentation and a predisposition to skin cancer [2,3]. In addition to the cutaneous manifestation, neurological abnormalities (loss of hearing, tendon refluxes, walking impairment, and intellectual impairment) are seen in 20% of patients with XP [4].…”

Section: Discussionmentioning

confidence: 99%

Life-Threatening Stridor in Xeroderma Pigmentosum Type A

Balsam¹

2016

JOENTR

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Vocal fold dystonia and total vocal fold paralysis in Xeroderma Pigmentosum Type-A (XPA) are rare clinical conditions that have been recently described in a few case reports from the Japanese literature. We report here an 11-year-old boy with XPA and seizures and a history of frequent emergency room (ER) visits to different local hospitals for recurrent inspiratory stridor that was treated as "croup" since the age of 10.

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The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm

Cited by 251 publications

References 0 publications

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

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

Biochemical and Structural Domain Analysis of Xeroderma Pigmentosum Complementation Group C Protein

Life-Threatening Stridor in Xeroderma Pigmentosum Type A

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