Human metabolism of arsenosugars

Recent epidemiological studies confirming that arsenic in drinking water can cause human cancers have lead to renewed concerns about the exposure of humans to arsenic through consumption of water and food. Some foods, in particular seafoods, contain high concentrations of arsenic, mostly bound into organoarsenic compounds which occur naturally in the environment. The major organoarsenic compound present in seafood is arsenobetaine, a non- toxic form of arsenic that presents no health risk to consumers. Arsenic-containing sugar compounds, called arsenosugars, constitute another major group of naturally-occurring arsenicals in seafoods. Preliminary testing of arsenosugars, however, suggests that they may be detrimental to health because they are converted in humans to potentially toxic arsenic species. The proposed project will investigate the processes effecting these changes. In particular, the project aims to identify and quantify the arsenic metabolites produced in humans and excreted in the urine after ingestion of arsenosugars, and to evaluate the individual variability in the way humans metabolise arsenosugars.Two arsenosugars, prepared and purified in the laboratory, will be individually administered in trace amounts to human volunteers, and the transformation of the compounds monitored by measuring the arsenic metabolites excreted in the urine. Analytical methods using separation systems connected to arsenic-specific detectors will enable the arsenosugar metabolites to be identified and specifically measured in the complex urine samples. Any arsenic compounds detected in the urine can be confidently assigned as arsenosugar metabolites since there will be no other source of arsenic to the volunteers. These experiments will be performed on a number of volunteers in order to assess the individual variability in the way humans metabolise arsenosugars, and investigate factors such as racial origin, sex and age. The properties of the arsenic metabolites will also be investigated to facilitate their future detection in biological samples. The study will be central to the evaluation of the potential risk to human health of arsenosugars naturally present in seafoods by providing detailed information about the quantities and chemical nature of the arsenic metabolites produced by humans consuming arsenosugars.

Recent epidemiological studies confirming that arsenic in drinking water can cause human cancers have lead to renewed concerns about the exposure of humans to arsenic through consumption of water and food. Some foods, in particular seafoods, contain high concentrations of arsenic, mostly bound into organoarsenic compounds which occur naturally in the environment. The major organoarsenic compound present in seafood is arsenobetaine, a non- toxic form of arsenic that presents no health risk to consumers. Arsenic-containing sugar compounds, called arsenosugars, constitute another major group of naturally-occurring arsenicals in seafoods. Preliminary testing of arsenosugars, however, suggests that they may be detrimental to health because they are converted in humans to potentially toxic arsenic species. The proposed project will investigate the processes effecting these changes. In particular, the project aims to identify and quantify the arsenic metabolites produced in humans and excreted in the urine after ingestion of arsenosugars, and to evaluate the individual variability in the way humans metabolise arsenosugars.Two arsenosugars, prepared and purified in the laboratory, will be individually administered in trace amounts to human volunteers, and the transformation of the compounds monitored by measuring the arsenic metabolites excreted in the urine. Analytical methods using separation systems connected to arsenic-specific detectors will enable the arsenosugar metabolites to be identified and specifically measured in the complex urine samples. Any arsenic compounds detected in the urine can be confidently assigned as arsenosugar metabolites since there will be no other source of arsenic to the volunteers. These experiments will be performed on a number of volunteers in order to assess the individual variability in the way humans metabolise arsenosugars, and investigate factors such as racial origin, sex and age. The properties of the arsenic metabolites will also be investigated to facilitate their future detection in biological samples. The study will be central to the evaluation of the potential risk to human health of arsenosugars naturally present in seafoods by providing detailed information about the quantities and chemical nature of the arsenic metabolites produced by humans consuming arsenosugars.