title: Influence of dietary selenium on the disposition of arsenate in the female B6C3F1 mouse.
abstract: Interactions between arsenic (As) and selenium (Se) at the metabolic level are multifaceted and complex. These interactions are of practical significance because populations in various parts of the world are simultaneously exposed to inorganic As in drinking water and Se mainly in the diet at varying levels. The primary goal of this study was to investigate whether differing dietary Se status would alter the profile of urinary metabolites or their time course for elimination after exposure to arsenate [As(V)]. Weanling female B6C3F1 mice were maintained for 28 d on either a control diet of powdered rodent meal sufficient in Se (A, 0.2 ppm) or Torula yeast-based (TYB) diets deficient (B, 0.02 ppm Se), sufficient (C, 0.2 ppm Se), or excessive (D, 2.0 ppm Se) in Se; mice then received by oral gavage 5 mg (As)/kg as sodium [73As] arsenate. The time course for elimination of total arsenic and metabolites in urine was measured over a 48-h period, and total arsenic was determined in feces and tissues at 48 h. Mice on the Se excess diet excreted a significantly higher percentage of urinary As as inorganic As, with a significantly decreased ratio of organic to inorganic As compared to Se-sufficient mice, suggesting that As methylation was decreased. Mice on the Se-deficient diet appeared to eliminate As(V), arsenite, and dimethylarsinic acid (DMA) in urine more slowly than Se-sufficient mice; however, further studies are required to confirm this finding. Mice on the Se-sufficient meal diet (A) excreted significantly less (by percent) arsenate-derived radioactivity in urine and more in feces compared to mice on the Se-sufficient TYB diet (C), with total elimination being similar for both groups. This indicates that mice on the meal diet absorbed significantly less As(V) than mice on the TYB diet, and this may be due to more fiber or "bulk" in the meal diet. This finding emphasizes the importance of considering dietary composition when interpreting and comparing As disposition studies. Overall this study provides suggestive evidence that dietary Se status alters As metabolism and disposition. This indicates that dietary Se status may be an issue that should be considered in the design and interpretation of epidemiologic studies.
authors.affiliation: Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park 27711-2055, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Kenyon
authors.forename: M F
authors.initials: MF
authors.lastname: Hughes
authors.forename: O A
authors.initials: OA
authors.lastname: Levander
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001149:Arsenates / Q000378:metabolism / Q000652:urine*; D001835:Body Weight / Q000187:drug effects; D002101:Cacodylic Acid / Q000378:metabolism / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004347:Drug Interactions; D005243:Feces / Q000737:chemistry; D005260:Female; D005527:Food, Fortified; D006540:Herbicides / Q000378:metabolism / Q000652:urine*; D007408:Intestinal Absorption / Q000187:drug effects; D007553:Isotope Labeling; D051379:Mice; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D001149:Arsenates; D006540:Herbicides; D013438:Sulfhydryl Compounds; D002101:Cacodylic Acid; D012643:Selenium; C025657:arsenic acid