title: Mechanisms of toxicity of triphenyltin chloride (TPTC) determined by a live cell reporter array.
abstract: 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.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse & School of the Environment, Nanjing University, Nanjing, China.
authors.forename: Guanyong
authors.initials: G
authors.lastname: Su
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Jason C
authors.initials: JC
authors.lastname: Raine
authors.forename: Liqun
authors.initials: L
authors.lastname: Xing
authors.forename: Eric
authors.initials: E
authors.lastname: Higley
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D004305:Dose-Response Relationship, Drug; D048168:Escherichia coli K12 / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005819:Genetic Markers; D049452:Green Fluorescent Proteins / Q000235:genetics; D009152:Mutagenicity Tests / Q000379:methods*; D009947:Organotin Compounds / Q000633:toxicity*; D011401:Promoter Regions, Genetic
chemical_list: D029968:Escherichia coli Proteins; D005819:Genetic Markers; C098049:GlgS protein, E coli; D009947:Organotin Compounds; C489586:wzzB protein, E coli; D049452:Green Fluorescent Proteins; C012594:triphenyltin chloride