Abstract
Although it is generally believed that the developing fetus is principally exposed to inorganic arsenic and the methylated metabolites from the maternal metabolism of arsenic, little is known about whether the developing embryo can autonomously metabolize arsenic. This study investigates inorganic arsenic methylation by murine embryonic organ cultures of the heart, lung, and liver. mRNA for AS3mt, the gene responsible for methylation of arsenic, was detected in all embryonic tissue types studied. In addition, methylated arsenic metabolites were generated by all three tissue types. The fetal liver explants yielded the most methylated arsenic metabolites (∼7% of total arsenic/48 h incubation) while the heart, and lung preparations produced slightly greater than 2% methylated metabolites. With all tissues the methylation proceeded mostly to the dimethylated arsenic species. This has profound implications for understanding arsenic-induced fetal toxicity, particularly if the methylated metabolites are produced autonomously by embryonic tissues.
Highlights
Several epidemiological studies show increase in human fetal and infant death as a result of chronic exposure to arsenic (Ahmad et al, 2001; Milton et al, 2005)
murine embryonic fibroblasts (MEF) were prepared in DMEM culture medium by serial passage through sterile 18 gauge and 25 gauge syringes: single cell suspensions were cultured, allowing cells to adhere and all experiments were performed in passage number 6 or less
3.1 To determine whether these select embryonic tissues can metabolize inorganic arsenic into methylated forms, primary tissues were exposed for 48 hr to various concentrations of As(III) and arsenic species determined
Summary
Several epidemiological studies show increase in human fetal and infant death as a result of chronic exposure to arsenic (Ahmad et al, 2001; Milton et al, 2005). Many human populations are exposed to a range of arsenic concentrations in the parts per billion (ppb) ranges over protracted periods of time including fetal development and early life. These are critical developmental periods for heart, lung, and liver, potentially making the development of these organ systems susceptible to effects of arsenic. In this regard, our laboratory reported mice exposed to 100 ppb As(III) in drinking water in utero (ED 6-term) developed non-alcoholic fatty liver disease as adults (Sanchez-Soria et al, 2014). Others have shown that in ApoE −/− mice, in utero drinking water exposure (ED 8term) to 49 parts per million (ppm) arsenite resulted in an inflammatory state in the adult liver (States et al 2012) as well as increased atherosclerosis (Srivastava et al 2007)
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