title: Photoreactivity of 5-fluorouracil under UVB light: photolysis and cytotoxicity studies.
abstract: The photodegradation of the chemotherapeutic agent 5-fluorouracil (5-FU) under UVB light was studied both in aqueous and methanol solutions and in systemic and topical formulations. As monitored by HPLC, photodegradation in solution takes place in a concentration dependent manner; thus, the solution for parenteral administration (10(-1) M) showed negligible loss of the active principle. On the contrary, the commercial cream containing 5% of 5-FU showed low stability under UVB exposure. When dissolved either in water or methanol, 5-FU yields two photoproducts which have been characterized as two isomers coming from the addition of the solvent to the 5,6 double bond of the drug. As a consequence, photomodified 5-FU loses its antiproliferative activity on HCT-15 and HeLa cells. MS analysis showed that photoaddition occurred with nucleophilic amino acids, such as cysteine and serine, while susceptible amino acids (cysteine and methionine) were oxidized. In fact, high production of the superoxide anion under UVB light as well as photooxidation of BSA suggests protein photodamage as a mechanism of photosensitization. Indeed, some phototoxicity was shown in experiments on NCTC keratinocytes and MCF-7 resistant cells irradiated with UVB light. The interactions with these biological targets may contribute to skin phototoxicity and photoallergy induced by 5-FU in vivo.
authors: Department of Pharmaceutical Sciences, University of Padova , Via Marzolo 5, 35131 Padova, Italy. giorgia.miolo@unipd.it
authors: Giorgia
authors: G
authors: Miolo
authors: Christine
authors: C
authors: Marzano
authors: Valentina
authors: V
authors: Gandin
authors: Angelo C
authors: AC
authors: Palozzo
authors: Daniele
authors: D
authors: Dalzoppo
authors: Alessia
authors: A
authors: Salvador
authors: Sergio
authors: S
authors: Caffieri
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D005472:Fluorouracil / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D007536:Isomerism; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects; D013058:Mass Spectrometry; D000432:Methanol / Q000737:chemistry; D010084:Oxidation-Reduction; D010782:Photolysis; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry
chemical_list: D000964:Antimetabolites, Antineoplastic; D014867:Water; D005472:Fluorouracil; D000432:Methanol