Modification of organometallic compound cytotoxicity by incorporated metal atoms and molecular mechanisms underlying the toxicity

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We have already found that organobismuth compounds often exhibit cytotoxicity in vascular endothelial cells. The purpose of the present study was to obtain cell clones that are tolerant to the toxic organobismuth compounds (PMTABi, DAPBi, and TDPBi) form a random gene trap insertional mutants library of CHO cells, to investigate candidate genes involved in the tolerance of the cells, and to clarify the molecular targets of the cytotoxicity of the organobismuth compounds. We succeeded to obtain 97 clones of the tolerant cells and identified candidate genes involved in the tolerance of the cells.