Photoprotective effect of isoflavone genistein on ultraviolet B-induced pyrimidine dimer formation and PCNA expression in human reconstituted skin and its implications in dermatology and prevention of cutaneous carcinogenesis.

2.50
Hdl Handle:
http://hdl.handle.net/10146/65059
Title:
Photoprotective effect of isoflavone genistein on ultraviolet B-induced pyrimidine dimer formation and PCNA expression in human reconstituted skin and its implications in dermatology and prevention of cutaneous carcinogenesis.
Authors:
Moore, Julian O.; Wang, Yongyin; Stebbins, William G.; Gao, Dayuan; Zhou, Xueyan; Phelps, Robert; Lebwohl, Mark; Wei, Huachen
Abstract:
Genistein, the most abundant isoflavone of the soy derived phytoestrogen compounds, is a potent antioxidant and inhibitor of tyrosine kinase. We previously reported the antiphotocarcinogenic effects of genistein in SKH-1 murine skin, including its capacity for scavenging reactive oxygen species, inhibiting photodynamic DNA damage and downregulating UVB(ultra violet B)-induced signal transduction cascades in carcinogenesis. In this study we elucidate genistein's photoprotective efficacy within the context of full thickness human reconstituted skin relative to acute challenges with ultraviolet-B irradiation. Skin samples were pre-treated with three concentrations of genistein (10, 20 and 50 microM) 1 h prior to UVB radiation at 20 and 60 mJ/cm2. Proliferating cell nuclear antigen (PCNA) and pyrimidine dimer (PD) expression profiles were localized using immunohistochemical analysis on paraffin embedded samples 6 and 12 h post UVB exposure. Genistein dose dependently preserved cutaneous proliferation and repair mechanics at 20 and 60 mJ/cm2, as evidenced by the preservation of proliferating cell populations with increasing genistein concentrations and noticeable paucity in PCNA immunoreactivity in the absence of genistein. Genistein inhibited UV-induced DNA damage, evaluated with PD immunohistochemical expression profiles, demonstrated an inverse relationship with increasing topical genistein concentrations. Irradiation at 20 and 60 mJ/cm2 substantially induced PD formation in the absence of genistein, and a dose dependent inhibition of UVB-induced PD formation was observed relative to increasing genistein concentrations. Collectively all genistein pre-treated samples demonstrated appreciable histologic architectural preservation when compared with untreated specimens. These findings represent a critical link between our animal and cell culture studies with those of human skin and represent the first characterization of the dynamic alterations of UV-induced DNA damage and proliferating cell populations relative to pretreatment with genistein in human reconstituted skin. The implications of our findings serve as compelling validation to our conclusions that genistein may serve as a potent chemopreventive agent against photocarcinogenesis.
Citation:
Carcinogenesis 2006, 27 (8):1627-3165
Journal:
Carcinogenesis
Issue Date:
Aug-2006
URI:
http://hdl.handle.net/10146/65059
DOI:
10.1093/carcin/bgi367
PubMed ID:
16522663
Additional Links:
http://carcin.oxfordjournals.org/cgi/content/full/27/8/1627
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: adverse effects;analysis;Anticarcinogenic Agents;Cells,Cultured;drug effects;Dermatology;dietary modulation of carcinogenesis-related pathways;Epidermis;Genistein;Humans;metabolism;New York;prevention & control;Proliferating Cell Nuclear Antigen;Pyrimidine Dimers;radiation effects;Skin;Skin Neoplasms;Skin,Artificial;therapeutic use;Ultraviolet Rays.
ISSN:
0143-3334
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorMoore, Julian O.-
dc.contributor.authorWang, Yongyin-
dc.contributor.authorStebbins, William G.-
dc.contributor.authorGao, Dayuan-
dc.contributor.authorZhou, Xueyan-
dc.contributor.authorPhelps, Robert-
dc.contributor.authorLebwohl, Mark-
dc.contributor.authorWei, Huachen-
dc.date.accessioned2009-04-16T12:35:48Z-
dc.date.available2009-04-16T12:35:48Z-
dc.date.issued2006-08-
dc.identifier.citationCarcinogenesis 2006, 27 (8):1627-3165en
dc.identifier.issn0143-3334-
dc.identifier.pmid16522663-
dc.identifier.doi10.1093/carcin/bgi367-
dc.identifier.urihttp://hdl.handle.net/10146/65059-
dc.descriptionKEYWORDS CLASSIFICATION: adverse effects;analysis;Anticarcinogenic Agents;Cells,Cultured;drug effects;Dermatology;dietary modulation of carcinogenesis-related pathways;Epidermis;Genistein;Humans;metabolism;New York;prevention & control;Proliferating Cell Nuclear Antigen;Pyrimidine Dimers;radiation effects;Skin;Skin Neoplasms;Skin,Artificial;therapeutic use;Ultraviolet Rays.en
dc.description.abstractGenistein, the most abundant isoflavone of the soy derived phytoestrogen compounds, is a potent antioxidant and inhibitor of tyrosine kinase. We previously reported the antiphotocarcinogenic effects of genistein in SKH-1 murine skin, including its capacity for scavenging reactive oxygen species, inhibiting photodynamic DNA damage and downregulating UVB(ultra violet B)-induced signal transduction cascades in carcinogenesis. In this study we elucidate genistein's photoprotective efficacy within the context of full thickness human reconstituted skin relative to acute challenges with ultraviolet-B irradiation. Skin samples were pre-treated with three concentrations of genistein (10, 20 and 50 microM) 1 h prior to UVB radiation at 20 and 60 mJ/cm2. Proliferating cell nuclear antigen (PCNA) and pyrimidine dimer (PD) expression profiles were localized using immunohistochemical analysis on paraffin embedded samples 6 and 12 h post UVB exposure. Genistein dose dependently preserved cutaneous proliferation and repair mechanics at 20 and 60 mJ/cm2, as evidenced by the preservation of proliferating cell populations with increasing genistein concentrations and noticeable paucity in PCNA immunoreactivity in the absence of genistein. Genistein inhibited UV-induced DNA damage, evaluated with PD immunohistochemical expression profiles, demonstrated an inverse relationship with increasing topical genistein concentrations. Irradiation at 20 and 60 mJ/cm2 substantially induced PD formation in the absence of genistein, and a dose dependent inhibition of UVB-induced PD formation was observed relative to increasing genistein concentrations. Collectively all genistein pre-treated samples demonstrated appreciable histologic architectural preservation when compared with untreated specimens. These findings represent a critical link between our animal and cell culture studies with those of human skin and represent the first characterization of the dynamic alterations of UV-induced DNA damage and proliferating cell populations relative to pretreatment with genistein in human reconstituted skin. The implications of our findings serve as compelling validation to our conclusions that genistein may serve as a potent chemopreventive agent against photocarcinogenesis.en
dc.language.isoenen
dc.relation.urlhttp://carcin.oxfordjournals.org/cgi/content/full/27/8/1627en
dc.subject.meshAnticarcinogenic Agents-
dc.subject.meshCells, Cultured-
dc.subject.meshDermatology-
dc.subject.meshEpidermis-
dc.subject.meshGenistein-
dc.subject.meshHumans-
dc.subject.meshProliferating Cell Nuclear Antigen-
dc.subject.meshPyrimidine Dimers-
dc.subject.meshSkin-
dc.subject.meshSkin Neoplasms-
dc.subject.meshSkin, Artificial-
dc.subject.meshUltraviolet Rays-
dc.titlePhotoprotective effect of isoflavone genistein on ultraviolet B-induced pyrimidine dimer formation and PCNA expression in human reconstituted skin and its implications in dermatology and prevention of cutaneous carcinogenesis.en
dc.typeArticleen
dc.identifier.journalCarcinogenesisen

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