Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment
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ORIGINAL PAPER
Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment Baowei Chen & Fenglin Cao & Chungang Yuan & Xiufen Lu & Shengwen Shen & Jin Zhou & X. Chris Le
Received: 19 October 2012 / Revised: 21 December 2012 / Accepted: 22 December 2012 / Published online: 15 January 2013 # The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL patients over three consecutive days. The patients received 10 mg arsenic trioxide each day via intravenous infusion. The saliva samples were analyzed using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. Monomethylarsonous acid and monomethylmonothioarsonic acid were identified along with arsenite, dimethylarsinic acid, monomethylarsonic acid, and arsenate. Arsenite was the predominant arsenic species, accounting for 71.8 % of total arsenic in the saliva. Following the arsenic infusion each day, the percentage of methylated arsenicals significantly decreased, possibly suggesting that the arsenic methylation process was saturated by
B. Chen and F. Cao contributed equally to this paper. Published in the topical collection Metallomics with guest editors Uwe Karst and Michael Sperling. B. Chen : X. Lu : S. Shen : X. C. Le (*) Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2G3, Canada e-mail: [email protected] F. Cao : J. Zhou (*) Department of Hematology, Harbin Medical University, Harbin, China e-mail: [email protected] C. Yuan School of Environmental Sciences and Engineering, North China Electric Power University, Baoding 071003 Hebei, China
the high doses immediately after the arsenic infusion. The temporal profiles of arsenic species in saliva following each arsenic infusion over 3 days have provided information on arsenic exposure, metabolism, and excretion. These results suggest that saliva can be used as an appropriate clinical biomarker for monitoring arsenic species in APL patients. Keywords Acute promyelocytic leukemia . Arsenic speciation . Saliva . Metabolism . Arsenic trioxide treatment
Introduction Acute promyelocytic leukemia (APL) is a distinctive subtype of acute myelocytic leukemia characterized by reciprocal translocations between chromosomes 15 and 17. Many clinical trials have demonstrated that both new and relapsed APL patients can achieve complete remission after arsenic trioxide treatment [1–7]. Generally, APL patients receive intravenous infusions of
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