title: Folic acid and its photoproducts, 6-formylpterin and pterin-6-carboxylic acid, as generators of reactive oxygen species in skin cells during UVA exposure.
abstract: Folic acid (FA) is the synthetic form of folate (vitamin B9), present in supplements and fortified foods. During ultraviolet (UV) radiation FA is degraded to 6-formylpterin (FPT) and pterin-6-carboxylic acid (PCA) which generate reactive oxygen species (ROS) and may be phototoxic. The aim of the present study was to investigate the production of ROS and phototoxicity of FA, FPT and PCA in skin cells during UVA exposure. The production of ROS and phototoxicity of FA, FPT and PCA were studied in the immortal human keratinocytes (HaCaT) and malignant skin cells (A431 and WM115) during UVA exposure. Increased ROS production and the photoinactivation of cells in vitro were observed during UVA exposure in the presence of FA, FPT and PCA. HPLC analysis revealed that 10 μM FA photodegradation was around 2.1 and 5.8-fold faster than that of 5 μM and 1 μM FA. Photodegradation of FA is concentration dependent, and even non-phototoxic doses of FA and its photoproducts, FPT and PCA, generate high levels of ROS in vitro. FA, FPT and PCA are phototoxic in vitro. The photodegradation of topical or unmetabolized FA during UV exposure via sunlight, sunbeds or phototherapy may lead to ROS production, to the cutaneous folate deficiency, skin photocarcinogenesis and other deleterious skin effects. Further studies are needed to confirm whether UV exposure can decrease cutaneous and serum folate levels in humans taking FA supplements or using cosmetic creams with FA.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway. Electronic address: asta.juzeniene@rr-research.no.
authors.forename: Asta
authors.initials: A
authors.lastname: Juzeniene
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway.
authors.forename: Mantas
authors.initials: M
authors.lastname: Grigalavicius
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway.
authors.forename: Li Wei
authors.initials: LW
authors.lastname: Ma
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway.
authors.forename: Marina
authors.initials: M
authors.lastname: Juraleviciute
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D005492:Folic Acid / Q000032:analysis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010782:Photolysis / Q000528:radiation effects; D011621:Pteridines / Q000032:analysis / Q000737:chemistry* / Q000633:toxicity; D011622:Pterins / Q000032:analysis / Q000737:chemistry* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D011621:Pteridines; D011622:Pterins; D017382:Reactive Oxygen Species; C405202:pterine-6-carboxylic acid; C005926:2-amino-4-hydroxy-6-formylpteridine; D005492:Folic Acid
keywords: 6-Formylpterin; Folic acid; Phototoxicity; Pterin-6-carboxylic acid; Reactive oxygen species; UVA radiation