Enteric bacteria may play a role in mammalian arsenic metabolism

Abstract

The cecal content of rats administered dimethylarsinic acid for 6 months via drinking water was cultured in GAM medium with 10 mg l À1 of dimethylarsinic acid. Arsenic compounds in the culture were analyzed by ion chromatography with inductively coupled plasma mass spectrometry (IC-ICP-MS). Dimethylarsinic acid was metabolized. Two bacterial Escherichia coli strains, A3-4 and A3-6, were isolated from the culture. These strains metabolized dimethylarsinic acid and yielded two unidentified arsenic compounds, M-2 and M-3. A3-6 methylated dimethylarsinic acid to trimethylarsine oxide. Both strains metabolized trimethylarsine oxide and yielded an unidentified arsenic compound, M-1. These unknown arsenic compounds were the same compounds as detected in the urine and the feces of rats administered dimethylarsinic acid. The strains reduced arsenate to arsenite efficiently. Cysteine was required for metabolism of dimethylarsinic acid by these bacteria, but glutathione was not required. These results strongly suggested that the intestinal bacteria have a different arsenic metabolism from that in mammals and that they may play a possible role in mammalian arsenic metabolism. Copyright INTRODUCTIONEpidemiological studies have indicated that arsenic is carcinogenic.1 However, the mechanism of induction of carcinogenesis by arsenic and the chemical form of the ultimate carcinogen is still unclear. The metabolism of arsenic in mammals is well known. When inorganic arsenic is introduced into the mammalian body, it is reduced to trivalent arsenic, and is methylated to monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) or trimethylarsine oxide (TMAO).2,3 Since DMA is the principal metabolite of inorganic arsenic in rat 4 and is supposed to be a carcinogen or a promoter, 5,6 it is important to study the metabolism of DMA.Some researchers have suggested the possibility of contribution of intestinal bacteria to the metabolism of arsenic in mammals. Intestinal bacteria of experimental animals are able to methylate inorganic and organic arsenic.7-9 On the other hand, it appears that bacterial metabolism of arsenic differs from mammalian metabolism. Cullen et al. 10 reported that intestinal bacteria in ceca of rats demethylate a methylated arsenic compound. Yoshida et al. 11,12 detected three unknown arsenic compounds in the urine and feces of rats administered DMA, TMAO or MMA. They suggested that these unknown arsenic compounds might be produced by intestinal bacteria, since elimination of the unknown compounds is greater in rats administered arsenics orally than in those administered it intraperitoneally. It is possible that these compounds are produced by intestinal bacteria and are related to the toxic effects of DMA in mammals.We examined the ability of culture of rat cecal content to yield unknown arsenic compounds from DMA, and attempted to isolate the bacteria metabolizing DMA.

Metabolism of dimethylarsinic acid in rats: production of unidentified metabolites in vivo

“…Further support for this hypothesis was recently obtained from the findings by Kuroda et al,42 which showed that DMA was converted to M-2 and M-3 in DMA-containing GAM medium with E. coli added under aerobic conditions and that TMAO was converted to M-1. 42 Kuroda et al 42 also reported that the conversion of DMA to M-2 and M-3 by E. coli in bouillon medium required cysteine, suggesting that cysteine was involved in the conversion of DMA to M-2 or M-3. Furthermore, it can be hypothesized that DMA or TMAO can be reduced to trivalent derivatives with cysteine in the presence of E. coli, resulting in the production of M-1, M-2, and M-3.…”

Microbial Methylation of Metalloids: Arsenic, Antimony, and Bismuth

“…Also becoming more widely used for nonvolatile organometalloid analysis are even more powerful so-called hyphenated instrumental techniques such as ion or HPLC-ICP-MS (110,141,147). And finally, the extraction of biological materials and subsequent determination of organoarsenicals has very recently been undertaken using microwave digestion followed by UV irradiation, hydride generation, and fluorescence spectrometry (244).…”

“…Thus, although GSH contributes to arsenic metabolism in animals, there may be a different metabolic pathway in bacteria (147).…”

An investigation of the effect of gastrointestinal microbial activity on oral arsenic bioavailability

“…However, only the SHIME incorporates the function of aerobic and anaerobic microorganisms present in the distal GI tract. [12] This could be of particular importance for estimating As bioaccessibility since GI microorganisms may influence As speciation, [13,14] thereby altering As toxicokinetics. [15] In addition, in vitro GI microbial activity Downloaded by [University of Nebraska, Lincoln] at 14:31 11 April 2015 often increases As bioaccessibility, as demonstrated for mine tailings, soils, and other test materials.…”