Alternative splicing of arsenic methyltransferase regulate arsenic toxicity

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In this study, we examined whether alternative splicing of arsenic methyltransferase (AS3MT) mRNA regulates arsenic toxicity.Exposure of arsenite to hepato-carcinoma HepG2 cells and human umbilical vein endothelial cells (HUVEC) resulted in an increase on the levels of splicing variant produced by exon-4 and -5 skipping (delta4,5).We next examined the levels of delta4,5 AS3MT mRNA in various cells. The results indicated that the levels of delta 4,5 in keratinocyte HaCaT cells, leukemia K562 cells and T-cells Jurkat cells were lower as compared with HepG2 and esophageal Het1A cells. In addition we compared the sensitivity to arsenite exposure between HepG2, HaCaT and Het1A cells. The results showed that the sensitivity to arsenite exposure was roughly equal in HaCaT and Het1A cells in spite of the difference of the levels of delta 4,5. These results suggested that the difference of sensitivity to arsenite in the various cells was no correlation with alternative splicing of AS3MT mRNA.