Broka Derrick, Ditzel Eric, Quach Stephanie, Camenisch Todd D
a Department of Pharmacology and Toxicology , Molecular and Cellular Biology, Bio5 Institute, and Southwest Environmental Health Sciences Center, University of Arizona , Tucson , AZ , USA.
Drug Chem Toxicol. 2016;39(3):279-83. doi: 10.3109/01480545.2015.1092043. Epub 2015 Oct 7.
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.
虽然人们普遍认为发育中的胎儿主要接触的是无机砷以及母体砷代谢产生的甲基化代谢产物，但对于发育中的胚胎是否能够自主代谢砷却知之甚少。本研究通过对小鼠心脏、肺和肝脏的胚胎器官培养来研究无机砷的甲基化。在所研究的所有胚胎组织类型中均检测到了负责砷甲基化的基因AS3mt的mRNA。此外，所有这三种组织类型都产生了甲基化砷代谢产物。胎儿肝脏外植体产生的甲基化砷代谢产物最多（约占总砷的7%/48小时孵育），而心脏和肺组织产生的甲基化代谢产物略高于2%。对于所有组织而言，甲基化主要生成二甲基化砷物种。这对于理解砷诱导的胎儿毒性具有深远意义，特别是如果甲基化代谢产物是由胚胎组织自主产生的话。
