Mechanisms of toxicity of triphenyltin chloride (TPTC) determined by a live cell reporter array

Su, Guanyong; Zhang, Xiaowei; Raine, Jason C.; Xing, Liqun; Higley, Eric; Hecker, Markus; Giesy, John P.; Yu, Hongxia

Mechanisms of toxicity of triphenyltin chloride (TPTC) determined by a live cell reporter array

2013

Triphenyltin chloride (TPTC), which has been extensively used in industry and agriculture, can occur at concentrations in the environment sufficient to be toxic. Here, potency of TPTC to modulate genes in a library containing 1,820 modified green fluorescent protein (GFP)-expressing promoter reporter vectors constructed from Escherichia coli K12 strains was determined. Exposure to TPTC resulted in 22 (fold change > 2) or 71 (fold change > 1.5) differentially expressed genes. The no observed transcriptional effect (NOTEC) and median transcriptional effect concentrations (TEC50) were determined to be 0.036 and 0.45 mg/L in E. coli. These responses were 1,230 and 97 times more sensitive than the acute median effect concentration (EC50) required to inhibit growth of cells, which demonstrated that this live cell array represents a sensitive method to assess toxic potency of chemicals. The 71 differentially expressed genes could be classified into seven functional groups. Of all the altered genes, three groups which encoded for catalytic enzymes, regulatory proteins, and structural proteins accounted for 28 %, 18 %, and 14 % of all altered genes, respectively. The pattern of differential expression observed during this study was used to elucidate the mechanism of toxicity of TPTC. To determine potential relationships among genes that were changed greater than 2.0-fold by exposure to TPTC, a correlation network analysis was constructed, and four genes were related to aroH, which is the primary target for metabolic regulation of aromatic biosynthesis by feedback inhibition in bacteria. The genes rnC, cld, and glgS were selected as potential biomarkers for TPTC, since their expression was more than 2.0-fold greater after exposure to TPTC.

اظهر المزيد [+]