Early molecular changes in the genome of arsenic-exposed human urothelial cells depending on cellular uptake and biotransformation

摘要

After uptake and disposition inorganic arsenic (As) may cause skin-, lung-, liver- and kidney-cancer as well as bladder tumors. Hereby As undergoes a biotransformation. Both the metabolic pathways and the role of As metabolism for As toxicity are currently the subject of intensive debate. The central site for As methylation in the human body is the liver. Urothelial cells do not methylate inorganic As. The mechanism of As-induced bladder cancer is not known so far. In our study we investigated early molecular changes in As-exposed human urothelial cells in dependence upon uptake and biotransformation of As. Beside the induction of DNA breakage, we analyzed miroRNA- and COX2-expression because these parameters are associated with bladder cancer.