Within the highly ascertained North-West England population, schwannomatosis has less than half the birth incidence and prevalence of NF2.
UVA should receive significant consideration as a human health risk as it is a large proportion of the solar spectrum that reaches the earth's surface and because of its ability to penetrate human skin. It is only relatively recently that this has been recognized and this previously under-researched part of the UV spectrum is becoming increasingly well characterized at doses that are quite low in relation to those experienced by humans. Absorption of UVA in a cell leads to the production of reactive oxygen and nitrogen species that can damage major biomolecules including DNA and membrane lipids. Various types of damage induced in these molecules lead to significant biological effects including cytotoxicity, mutations and alterations in cell signalling pathways. Longer-term effects such as persistent genomic instability and bystander effects have also been observed following UVA treatment of mammalian cells and, as with ionizing radiation, this changes some of the fundamental thinking around tissue effects of irradiation. Antioxidants have been assessed extensively for their ability to protect against the biological effects of UVA and a number have been shown to be successful at least in-vitro, for example vitamin E and epigallocatechin-3-gallate. Other potential targets for protection are suggested through the increased understanding of some of the signalling mechanisms activated following treatment, for example the inhibition of NADPH oxidase is seen to reduce a bystander effect. The search for appropriate and successful photoprotective agents remains an important area of research.
A number of biological activities have been ascribed to the major green tea polyphenol epigallocatechin-3-gallate (EGCG) to explain its chemopreventive properties. Its antioxidant properties emerge as a potentially important mode of action. We have examined the effect of EGCG treatment on the damaging oxidative effects of UVA radiation in a human keratinocyte line (HaCaT). Using the ROS-sensitive probes dihydrorhodamine 123 (DHR) and 2 ,7 -dichlorodihydrofluorescein diacetate (DCFH-DA), we detected a reduction in fluorescence in UVA-irradiated (100 kJ/m 2 ) cells in the case of the former but not the latter probe after a 24-hr treatment with EGCG (e.g., 14%, [p < 0.05] after 10 M EGCG). In the absence of UVA, however, both DHR and DCFH detected a pro-oxidant effect of EGCG at the highest concentration used of 50 M. Measurements of DNA damage in UVA-exposed cells using the single cell gel electrophoresis assay (comet assay) also showed the protective effects of EGCG. A concentration of 10 M EGCG decreased the level of DNA single strand breaks and alkali-labile sites to 62% of the level observed in non-EGCG, irradiated cells (p < 0.001) with a 5-fold higher concentration producing little further effect. Correspondingly, EGCG ablated the mutagenic effects of UVA (500 kJ/m 2 ) reducing an induced hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutant frequency of (3.39 ؎ 0.73) ؋ 10 ؊6 to spontaneous levels (1.09 ؎ 0.19) ؋ 10 ؊6 . Despite having an antiproliferative effect in the absence of UVA, EGCG also served to protect against the cytotoxic effects of UVA radiation. Our data demonstrate the ability of EGCG to modify endpoints directly relevant to the carcinogenic process in skin. © 2002 Wiley-Liss, Inc. Key words: epigallocatechin-3-gallate; antioxidant; ultraviolet AThere has been considerable recent interest in the chemopreventive properties of the polyphenols or catechins of green tea that have been shown to inhibit tumorigenesis in a variety of organs in rodent models. 1-3 The major polyphenol component by mass, (Ϫ)-epigallocatechin-3-gallate (EGCG) is an effective protectant against the mutagenicity of a number of chemical carcinogens including benzo[a]pyrene (B[a]P), aflatoxin B1 and 3-hydroxyamino-1-methyl-5H-pyrido [4,3-b]indole. 4 -6 EGCG, together with other green tea polyphenols also exhibits growth inhibitory properties in a variety of tumour cell lines. 7-9 Several mechanisms have been proposed by which these compounds exert their anti-tumorigenic action: these include the blockade of growth factors binding to their receptors, 10 phosphorylation (activation) of mitogen-activated protein kinases (MAPKs) 11,12 possibly resulting in the observed induction of Phase II drug-metabolizing enzymes, 13,14 and the generation of oxidative stress leading to apoptosis. 7,9 In the face of an oxidative challenge, however, it is now well documented that green tea catechins act as antioxidants. For example, EGCG abrogates oxidation by hydrogen peroxide both in a cell free system 15 and in terms of DNA single-s...
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