title: [Enhancement of endogenous antioxidant defenses: a promising strategy for prevention of skin cancers].
abstract: There is considerable evidence that ultraviolet radiation (UV) from sunlight is implicated in skin carcinogenesis. So the risks of cutaneous cancer have increased during the last decade due to increase of sun exposure. For a long time, ultraviolet B radiation (UVB: 290-320 nm) have been considered to be the more efficient wavelength in eliciting carcinogenesis in human skin. It is today clear that UVA (320-400 nm), especially UVA1 (340-400 nm) also participate to photo carcinogenesis. One of molecular mechanisms in the biological effects of UV is the induction of reactive oxygen species (ROS) directly or through endogenous photosensitization reactions. UVA radiation mainly acts via this production of ROS and the subsequent oxidative stress seems to play a crucial role in the deleterious effects of UVA. Fortunately, the skin possesses a wide range of interlinked antioxidant defence mechanism to protect itself from damage by UV-induced ROS. However, the capacity of these systems is not unlimited; they can be overwhelmed by excessive exposure to UV and then ROS can reach damaging levels. An interesting strategy to provide photoprotection would be to support or enhance one or more of these endogenous systems. In our experiments, we have evaluated the protective effect of glutathion, selenium and zinc, three compounds playing a pivotal role in the cellular defence against oxidative damage. We have irradiated both by UVA1 and UVB culture of human normal skin fibroblasts or of spontaneously immortalised human keratinocyte cell line Hacat. Before irradiation, treated cells were submitted to zinc deprivation by a diffusible zinc chelator, NNN' N'-tetrakis (2-pyridylmethyl) ethylene diamine (TPEN) or supplied with zinc chloride, thiols (N-acetyl-cysteine; N-acetyl-homocysteine-thiolactone, L2oxothiozolidine-4 carboxylate) selenium as sodium selenite. The cell viability was measured using the adhesion-proliferation method or a tetrazolium colorimetric assay. The damages induced to cellular membrane were appreciated by determination of thiobarbituric reactants (Tbars) by a fluorometric micromethod. Cellular DNA damage was examined by strand break determination carried out using the method described by Birnboim and Jevcak and by the Comet assay. Our results show that: UVA1 have a main part in cytotoxic effect of UVA and this effect is linked to ROS; thiols and selenium protect cells against UVA radiation with a synergic interaction and this protection acts though an increase in glutathion peroxidase activity; zinc protects against cytotoxicity of UVA and UVB and against UVB induced DNA damages; above all, DNA damages induced by UVA or UVB are significantly prevented by thiol molecules, selenium and zinc. As DNA damages have a main place in photocarcinogenesis, our results point out the potential interest of a photoprotection based on the support of endogenous antioxidant system. The research of new ways for photoprotection is indeed a necessity because sunscreens did not give convincing evidences of efficacy in preventing skin cancers.
authors.affiliation: Département Pluridisciplinaire de Médecine, Dermatologie, Hôpital A. Michallon, BP 217 X-38043 Grenoble.
authors.forename: J C
authors.initials: JC
authors.lastname: Béani
mesh_terms: D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D018929:Cell Culture Techniques; D002460:Cell Line; D004249:DNA Damage; D005347:Fibroblasts / Q000502:physiology*; D005978:Glutathione / Q000494:pharmacology* / Q000627:therapeutic use; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress; D012643:Selenium / Q000494:pharmacology* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000517:prevention & control*; D013473:Sunscreening Agents; D014466:Ultraviolet Rays / Q000009:adverse effects; D015032:Zinc / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D013473:Sunscreening Agents; D005979:Glutathione Peroxidase; D005978:Glutathione; D012643:Selenium; D015032:Zinc