Synopsis of: Formation of Methylated Oxyarsenical and Thioarsenicals in Wildtype and Arsenic (+3 Oxidation State) Methyltransferase Knockout Mice Exposed to Arsenate. Introduction

Synopsis of: Formation of methylated oxyarsenical and thioarsenicals in wildtype and arsenic (+3 Oxidation State) Methyltransferase knockout mice exposed to arsenate.
Arsenic is acknowledged as a worldwide toxicant leading to detrimental health effects ranging from severe effects on the gastrointestinal system to cancers of the urinary bladders, lungs and skin.   Regardless of the massive amount of studies done on arsenic, there have been no definitive understanding of the mechanism that underlie its adverse effects.   The metabolism of inorganic arsenic (iAs) is centered on the conversions of methylated metabolites.   Ingestion of iAs is followed by the excretions of (MMAV), (DMAIII) and DMAV.   Methylation of iAs to metabolites can cause health affects due to the fact that these arsenical can be more cytotoxic and genotoxic.   The metabolisms of iAs to methylated metabolites are catalyzed for an enzyme known as methyltransferase (As3mt).   Recent models for (As3mt) methylations assume that oxyarsenical, and thioarsenical such as (DMMTAV), (MMTAV), and (DMDTAV), are produced in humans and mammals.   The purpose of this study is to compare the patterns of methylated oxy- and thioarsenicals in the livers and urine of (As3mt) KO Mice and Wild type mice after a single oral dose of inorganic arsenic.
Materials and Methods
Preparation of (DMMTAV), (MMTAV), and (DMDTAV):   (MMTAV) was prepared with an unique step by step protocol involving the addition of concentrated HsSO4 and Na2S to and aqueous solution of (MMAV) to reach a (MMTAV)/ HsSO4/Na2S molar ratio of 1:2:3.   (DMMTAV) was prepared in a similar format.   An aqueous concentration of (DMAV) was mixed with HsSO4 and Na2S to reach a (DMMTAV)/ HsSO4/Na2S molar ratio of 1:1.6:1.6.   Lastly (DMDTAV) was formed by mixing an aqueous solution of (DMAV) with HsSO4 and Na2S to reach a final (DMAV)/ HsSO4/Na2S molar ratio of 1:7.5:7.5
Origin, maintenance and dosing of   (As3mt) KO Mice and wild-type:   Female and Male...