title: Arsenite medicinal use, metabolism, pharmacokinetics and monitoring in human hair.
abstract: Acute promyelocytic leukaemia (APL) is a distinctive subtype of acute myeloid leukaemias. Even through this human disease can be treated by the intravenous administration of all-trans retinoic acid (ATRA), 25% of patients typically relapse after the first treatment. In this context, the intravenous administration of APL patients with an aqueous solution of arsenic trioxide has also been demonstrated to be successful despite the established mammalian toxicity of this arsenic compound. Accordingly, the administration of a therapeutic dose of arsenic trioxide has resulted in an improved patient survival in both relapsing as well newly diagnosed APL patients. We present here a mini-review of the medicinal use of arsenite, its mammalian metabolism (with an emphasis on biomethylation pathways), its elimination and pharmacokinetics and the novel application of hair analysis as a biomonitoring material. This mini-review also introduces our own results on the analysis of hair of patients receiving arsenic trioxide therapy. In this work, instead of quantifying arsenic content in bulk hair, we performed longitudinal analysis in order to use hair as a marker of arsenic exposure correlated to a time scale. Taking into account the hair growth rate, the longitudinal analysis of hair is demonstrated to provide a chronological record of the treatment of patients with arsenic trioxide. The small quantity of material to be analysed required the use of Synchrotron radiation based X-ray fluorescence (SXRF) spectroscopy. The hair arsenic content was well correlated with the clinical background of patients and reflected the intake of arsenic trioxide. In particular, the onset of arsenic trioxide therapy and interruptions during therapy were reflected by total arsenic content, which suggested rapid elimination. Another type of experiment, micro-XRF cartography on thin hair slices, allowed us to obtain distribution maps of arsenic, which demonstrated that arsenic is located at the periphery of hair. Micro-XANES spectra recorded at the periphery of hair, suggest that inorganic arsenic is incorporated in hair in its trivalent oxidation state, in agreement with previous results.
authors.affiliation: Laboratoire de Biomathématiques, EA 2498, Département de Santé Publique et Biostatistiques, Plateau iB(2), Faculté de Pharmacie, Université Paris Descartes, Paris, France. ioannis.nicolis@parisdescartes.fr
authors.forename: I
authors.initials: I
authors.lastname: Nicolis
authors.forename: E
authors.initials: E
authors.lastname: Curis
authors.forename: P
authors.initials: P
authors.lastname: Deschamps
authors.forename: S
authors.initials: S
authors.lastname: Bénazeth
mesh_terms: D018053:Arsenites / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006197:Hair / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D013052:Spectrometry, X-Ray Emission
chemical_list: D018053:Arsenites; C015001:arsenite