Low-Dose Arsenic Trioxide Modulates the Differentiation of Mouse Embryonic Stem Cells

Chemical Research in Toxicology
Wenlin YuanZhi Huang

Abstract

Arsenic (As) is a well-known environmental pollutant, while arsenic trioxide (ATO) has been proven to be an effective treatment for acute promyelocytic leukemia, however, the mechanism underlying its dual effects is not fully understood. Embryonic stem cells (ESCs) exhibit properties of stemness and serve as a popular model to investigate epigenetic modifiers including environmental pollutants. Herein, the effects of low-dose ATO on differentiation were evaluated in vitro using a mouse ESCs (mESCs) cell line, CGR8. Cells treated with 0.2-0.5 μM ATO for 3-4 days had slight inhibition of proliferation with elevation of apoptosis, but obvious alterations of differentiation by morphological checking and alkaline phosphatase (AP) staining. Moreover, ATO exposure significantly decreased the mRNA expression of the stemness maintenance genes including Oct4, Nanog, and Rex-1 ( P < 0.01), whereas obviously increased some tissue-specific differentiation marker genes such as Gata4, Gata-6, AFP, and IHH. These alterations were consistent with the differentiation phenotype induced by retinoic acid (RA) and the expression patterns of distinct pluripotency markers such as SSEA-1 and Oct4. Furthermore, low-dose ATO led to a quantitative increas...Continue Reading

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