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IN VITRO BIOTRANSFOMATION OF AN ARSENOSUGAR BY MOUSE ANAEROBIC CECAL MICROFLORA AND CECAL TISSUE EXAMINED USING IC-ICP-MS AND LC-ESI-MS/MS
Citation:
CONKLIN, S., P. A. CREED, AND JOHN T. CREED. IN VITRO BIOTRANSFOMATION OF AN ARSENOSUGAR BY MOUSE ANAEROBIC CECAL MICROFLORA AND CECAL TISSUE EXAMINED USING IC-ICP-MS AND LC-ESI-MS/MS. ANALYST. Royal Society of Chemistry, Cambridge, Uk, 131(5):648-655, (2006).
Impact/Purpose:
The goal is to develop an extraction protocol that mimics the human digestive tract and then to use it to assess the bioavailable fraction of arsenic from complex dietary mixtures such as a daily composite -- to move current methods toward a better human physiologically-based exposure estimate method which approximates the "true" bioavailability of arsenic within an environmental or dietary matrix.
Description:
This investigation examined chemical and microbiological transformations of an arsenosugar by mouse cecum. To mimic the low oxygen environment in the mammalian gastrointestinal tract, reaction mixtures were incubated under anaerobic conditions. An arsenosugar extracted from ribbon kelp, 3-[5-deoxy-5-(dimethylarsinoyl)-ß-ribofuranosyloxy-2-hydroxypropanesulfonic acid, As(392), was added to reaction mixtures that contained either cecal microflora or cecal tissue homogenate. These reaction mixtures were incubated at 0 or 37°C for up to 48 hours to monitor biotransformation of the arsenosugar. Analysis of the reaction mixtures by IC-ICP-MS and LC-ESI-MS/MS indicated that the arsenosugar was converted primarily (95%) to its sulfur analog in less than 1 h at 37°C. Conversion of As(392) to its sulfur analog was much slower at 0°C (21% conversion after 48 h). In reaction mixtures with cecal tissue homogenate, conversion of As(392) to its sulfur analog was slower (77% conversion after 48 h at 37°C). A good mass balance was found in all reaction mixtures between the amount of arsenosugar added and the sum of all detected arsenic-containing products. LC-ESI-MS/MS spectra of the sulfur-containing arsenosugar formed in all reaction mixtures containing cecal microflora compared well with those of a synthetic standard. These results suggest that the anaerobic microflora of the gastrointestinal tract can rapidly convert ingested arsenosugars to sulfur analogs. This biotransformation may affect the subsequent absorption, metabolism, and disposition of arsenic present in arsenosugars.This investigation examined chemical and microbiological transformations of an arsenosugar by mouse cecum. To mimic the low oxygen environment in the mammalian gastrointestinal tract, reaction mixtures were incubated under anaerobic conditions. An arsenosugar extracted from ribbon kelp, 3-[5-deoxy-5-(dimethylarsinoyl)-ß-ribofuranosyloxy-2-hydroxypropanesulfonic acid, As(392), was added to reaction mixtures that contained either cecal microflora or cecal tissue homogenate. These reaction mixtures were incubated at 0 or 37°C for up to 48 hours to monitor biotransformation of the arsenosugar. Analysis of the reaction mixtures by IC-ICP-MS and LC-ESI-MS/MS indicated that the arsenosugar was converted primarily (95%) to its sulfur analog in less than 1 h at 37°C. Conversion of As(392) to its sulfur analog was much slower at 0°C (21% conversion after 48 h). In reaction mixtures with cecal tissue homogenate, conversion of As(392) to its sulfur analog was slower (77% conversion after 48 h at 37°C). A good mass balance was found in all reaction mixtures between the amount of arsenosugar added and the sum of all detected arsenic-containing products. LC-ESI-MS/MS spectra of the sulfur-containing arsenosugar formed in all reaction mixtures containing cecal microflora compared well with those of a synthetic standard. These results suggest that the anaerobic microflora of the gastrointestinal tract can rapidly convert ingested arsenosugars to sulfur analogs. This biotransformation may affect the subsequent absorption, metabolism, and disposition of arsenic present in arsenosugars.