Buxtehude, Germany
Buxtehude, Germany

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Greinert R.,Dermatology Center Buxtehude | Volkmer B.,Dermatology Center Buxtehude | Henning S.,Dermatology Center Buxtehude | Breitbart E.W.,Dermatology Center Buxtehude | And 4 more authors.
Nucleic Acids Research | Year: 2012

UVA (320-400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G1-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer. © 2012 The Author(s).


Greinert R.,Dermatology Center Buxtehude | Greinert R.,ADP | Boniol M.,International Prevention Research Institute
Progress in Biophysics and Molecular Biology | Year: 2011

Solar and artificial (sunbed) UV-exposure is the main risk factor for the development of epithelial skin cancer (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC) as well for malignant melanoma (MM). UV exposure in childhood and adolescence is especially important. Therefore, adequate methods of primary prevention have continuously to be used and to be developed further to target these age-groups in order to reduce the risks of intensive UV-exposure. Primary prevention can effectively be combined with secondary prevention (early detection, screening) to reduce the burden of skin cancer and to decrease incidence, morbidity and mortality. © 2011 Elsevier Ltd.


Volkmer B.,Dermatology Center Buxtehude | Greinert R.,Dermatology Center Buxtehude
Progress in Biophysics and Molecular Biology | Year: 2011

There is indicative epidemiological evidence that exposures of children younger than about 10 years are linked with an increased risk of the development of malignant melanoma as well as non-melanocytic skin cancers later in life. However, an important area of uncertainty relates to lack of knowledge of the sun-sensitivity of children's skin both absolutely and relative to that of adult's skin. For example the thickness of children's skin is very similar to that of adults but due to the nature of the anatomical structure of children's skin, there are indications of children's skin being adversely exposed on the top of the papilla before a significant exposure manifests itself as visible damage to the skin (for example erythema). This might also affect the induction of heavily UV-damaged cells persisting in the basal layer of the epidermis after UV-exposure which are supposed to be keratinocytic epidermal stem cells and may characterize an initiation step of non-melanoncytic skin cancer. For malignant melanoma the number of nevi received in dependence of UV-exposure in childhood is a clear risk factor. Recent data show that the bulge region of hair follicles hosting melanocytic stem cells are located deeper (more protected) in the skin in adults (terminal hair) as compared to pre-pubertal children (vellus hair). This may be an explanation for enhanced risk of malignant melanoma due to UV-exposure in pre-pubertal childhood. © 2011 Elsevier Ltd.


PubMed | Dermatology Center Buxtehude
Type: Journal Article | Journal: Progress in biophysics and molecular biology | Year: 2011

There is indicative epidemiological evidence that exposures of children younger than about 10 years are linked with an increased risk of the development of malignant melanoma as well as non-melanocytic skin cancers later in life. However, an important area of uncertainty relates to lack of knowledge of the sun-sensitivity of childrens skin both absolutely and relative to that of adults skin. For example the thickness of childrens skin is very similar to that of adults but due to the nature of the anatomical structure of childrens skin, there are indications of childrens skin being adversely exposed on the top of the papilla before a significant exposure manifests itself as visible damage to the skin (for example erythema). This might also affect the induction of heavily UV-damaged cells persisting in the basal layer of the epidermis after UV-exposure which are supposed to be keratinocytic epidermal stem cells and may characterize an initiation step of non-melanoncytic skin cancer. For malignant melanoma the number of nevi received in dependence of UV-exposure in childhood is a clear risk factor. Recent data show that the bulge region of hair follicles hosting melanocytic stem cells are located deeper (more protected) in the skin in adults (terminal hair) as compared to pre-pubertal children (vellus hair). This may be an explanation for enhanced risk of malignant melanoma due to UV-exposure in pre-pubertal childhood.


PubMed | Dermatology Center Buxtehude
Type: Journal Article | Journal: Progress in biophysics and molecular biology | Year: 2011

Solar and artificial (sunbed) UV-exposure is the main risk factor for the development of epithelial skin cancer (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC) as well for malignant melanoma (MM). UV exposure in childhood and adolescence is especially important. Therefore, adequate methods of primary prevention have continuously to be used and to be developed further to target these age-groups in order to reduce the risks of intensive UV-exposure. Primary prevention can effectively be combined with secondary prevention (early detection, screening) to reduce the burden of skin cancer and to decrease incidence, morbidity and mortality.


PubMed | Dermatology Center Buxtehude
Type: Journal Article | Journal: Nucleic acids research | Year: 2012

UVA (320-400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and H2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G(1)-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of H2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer.

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