UV-induced skin damage

doi:10.1016/S0300-483X(03)00150-1

Toxicology

Volume 189, Issues 1–2, 15 July 2003, Pages 21-39

https://doi.org/10.1016/S0300-483X(03)00150-1 Get rights and content

Abstract

Solar radiation induces acute and chronic reactions in human and animal skin. Chronic repeated exposures are the primary cause of benign and malignant skin tumors, including malignant melanoma. Among types of solar radiation, ultraviolet B (290–320 nm) radiation is highly mutagenic and carcinogenic in animal experiments compared to ultraviolet A (320–400 nm) radiation. Epidemiological studies suggest that solar UV radiation is responsible for skin tumor development via gene mutations and immunosuppression, and possibly for photoaging. In this review, recent understanding of DNA damage caused by direct UV radiation and by indirect stress via reactive oxygen species (ROS) and DNA repair mechanisms, particularly nucleotide excision repair of human cells, are discussed. In addition, mutations induced by solar UV radiation in p53, ras and patched genes of non-melanoma skin cancer cells, and the role of ROS as both a promoter in UV-carcinogenesis and an inducer of UV-apoptosis, are described based primarily on the findings reported during the last decade. Furthermore, the effect of UV on immunological reaction in the skin is discussed. Finally, possible prevention of UV-induced skin cancer by feeding or topical use of antioxidants, such as polyphenols, vitamin C, and vitamin E, is discussed.

Introduction

Chronic repeated exposures to sunlight from childhood are epidemiologically shown to be the main cause of skin cancers. Ultraviolet B radiation (UVB), a minor component of sunlight reaching to the earth surface, is experimentally demonstrated to be the most effective light to induce skin cancer in animals, and can cause DNA damage, particularly cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts which induce mutation in the epidermal cells, leading to the development of cancer cells.

UVB is also known to upregulate gene expression through intracellular signal transduction pathways, which may contribute to developing skin cancer at the tumor promotion stage. In addition, UVB is proved to suppress immune reaction, and to induce tolerance to antigens, which had been applied topically or systemically in experimental animals. These three effects of UVB on the skin are understood to cooperatively contribute to producing skin cancer in humans.

Ultraviolet light A (UVA) and UVB radiation are proved to produce DNA damage directly and indirectly through oxidative stress. Further, reactive oxygen species (ROS) are shown to activate transcription factors, such as AP-1 and NFkB, which may contribute to cell proliferation and/or apoptotic cell death. In this review, roles of ROS for UV-induced skin cancer development and possible preventive effects of antioxidants on UV-carcinogenesis are discussed.

Section snippets

DNA damage caused by UV radiation and ROS

The most cytotoxic and mutagenic waveband among types of solar radiation corresponds to UVB light. DNA bases directly absorb incident photons within this narrow wavelength range. The phototoxic effect of UVA radiation is much lower than UVB radiation. DNA is not a chromophore for UVA radiation (Rosenstein and Mitchell, 1987), but could be damaged by photosensitization reaction initiated through absorption of UVA by unidentified chromophore.

DNA repair mechanisms in human skin

Important mechanisms in human cells to avoid the potential mutation in UV-induced-damaged sites are to completely repair the damage by nucleotide excision repair (NER) before replication, or synthesize DNA using postreplication repair specific DNA polymerase which is free from error. NER is a highly conserved strategy for repairing a variety of bulky DNA damages, such as CPDs and (6–4) pp (Mitchell et al., 1985, Wood, 1997). Base change, such as 8-OHdG, is repaired by base excision repair (BER)

Mutations induced by UVB in NMSC cells

The general understanding of carcinogenic mechanisms is the hypothesis of clonal expansion of a cell having mutations of oncogenes and tumor suppressor genes (Rees, 1994). Oncogenes and tumor suppressor genes are suggested to have crucial roles on the control of the cell cycle, maintenance of gene integrity, cell proliferation and differentiation. These genes are also categorized into two groups, gatekeeper genes which usually control cellular proliferation and regulate apoptosis, such as Rb,

Activation of MAP kinase

Ultraviolet radiation is a potent inducer of superoxide radical (O₂⁻), hydrogen peroxide (H₂O₂) and hydroxy radical (OH), which have been implicated in cutaneous aging including benign and malignant tumors, and various inflammatory disorders (Cerutti, 1985). UVB may produce O₂⁻, and UVA may produce ¹O₂ possibly through chromophores, such as porphyrin in skin. Devary et al. (1992) showed that by UVC radiation, tyrosine kinases of the Src family increase, followed by activation of Ha-ras and

Local and systemic immunosuppression

UVB at high doses and even such a low level as one minimal erythema dose (MED) can impair host immune surveillance for skin cancers in rodents possibly by modulating the expression of co-stimulatory function of epidermal Langerhans cells (LCs) and lymphocytes. Initially, Fisher and Kripke (1997) described that skin tumors developed in adult mice exposed to high dose of UVB radiation for prolonged periods of time were rejected when transplanted to syngenic healthy mice, but continued to grow

Green tea and black tea

Green tea is one of the most common beverages in the Asia. The principal chemical constituents of green tea are polyphenols, containing (−)-epigallocatechin (EGC), (−)-epicatechin (EC), (−)-epicatechin-3-gallate (ECG) and (−)-epigallocatechin-gallate (EGCG) (Wang et al., 1992, Yang and Wang, 1993). These components are shown to react with cytochrome P450 and inhibit catalytic activities in a dose dependent manner.

Epidemiological studies in Asian countries showed that high green tea consumers

Conclusion

Skin cancers are mostly caused by chronic exposure to solar radiation, which induces activation of oncogenes and inactivation of tumor suppressorgenes. In addition, solar ultraviolet radiation stimulates cell proliferation via signal transduction initiated on cellular membrane. UVB and possibly UVA suppress immune responses, contributing to the development of skin cancer.

In this review, we discussed a role of UV-induced DNA damage in skin carcinogenesis and also recent advances in the

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UV-induced skin damage

Abstract

Introduction

Section snippets

DNA damage caused by UV radiation and ROS

DNA repair mechanisms in human skin

Mutations induced by UVB in NMSC cells

Activation of MAP kinase

Local and systemic immunosuppression

Green tea and black tea

Conclusion

Cell

J. Dermatol. Sci.

J. Invest. Dermatol.

Methods Enzymol.

J. Biol. Chem.

J. Invest. Dermatol.

Mutat. Res.

J. Photochem. Photobiol.

Cell

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Cell

Mol. Biol. Cell

J. Invest. Dermatol.

Trends. Mol. Med.

Mutat. Res.

J. Invest. Dermatol.

J. Invest. Dermatol.

J. Invest. Dermatol.

J. Biol. Chem.

J. Biol. Chem.

Free Radic. Biol. Med.

J. Invest. Dermatol.

J. Invest. Dermatol.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Invest. Dermatol.

J. Biol. Chem.

Cell

Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue

Cancer Res.

Indentification of the molecular target for the suppression of contact hypersensitivity by UV radiation

J. Exp. Med.

Ultraviolet light induces apoptosis via direct activation of CD95 (Fas/APO-1) independently of its ligand CD95L

J. Cell Biol.

Formation of 8-hydroxydeoxyguanosine within DNA of mouse keratinocytes exposed in culture to UVB and H2O2

Carcinogenesis

Regulation of tumor antigen presentation by urocanic acid

J. Immunol.

DNA repair in an active gene: removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall

Cell

A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma

Proc. Natl. Acad. Sci. USA

Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion

J. Invest. Dermatol. Symp. Proc.

Protective effect of topically applied olive oil against photocarcinogenesis following UVB exposure of mice

Carcinogenesis

Prooxidant states and tumor promotion

Science

Inositol hexaphosphate inhibits ultraviolet B-induced signal transduction

Mol. Carcinog.

Defective repair replication of DNA in xeroderma pigmentosum

Nature

Xeroderma pigmentosum and Cockayne syndrome

Correlation of UVC and UVB cytotoxicity with the induction of specific photoproducts in T-lymphocytes and fibroblasts from normal human donors

Photochem. Photobiol.

UV activation of receptor tyrosine kinase activity

Oncogenesis

Activation of the transcription factor Gli1 and the Sonic hedgehog signaling pathway in skin tumours

Nature

Nucleotide excision repair and human syndromes

Carcinogenesis

Specific protein kinase C isozymes mediate the induction of keratinocyte differentiation markers by calcium

Cell Growth Differ.

The mammalian ultraviolet response is triggered by activation of src tyrosine kinases

Cell

Formation of 8-hydroxydeoxyguanosine within DNA of mouse keratinocytes exposed in culture to UVB and H₂O₂