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MUTATIONAL AND TRANSCRIPTIONAL RESPONSES OF SAMMONELLA TO MX: CORRELATION OF MUTATIONAL DOSE RESPONSE TO CHANGES IN GENE EXPRESSION
Citation:
Ward, W. O., S. Porwollik, S H. Warren, M. McClelland, AND D. M. DEMARINI. MUTATIONAL AND TRANSCRIPTIONAL RESPONSES OF SAMMONELLA TO MX: CORRELATION OF MUTATIONAL DOSE RESPONSE TO CHANGES IN GENE EXPRESSION. Presented at Environmental Mutagen Society, Pittsburgh, PA, Oct, 2-6, 2004.
Description:
We measured the mutational and transcriptional response of Salmonella TA 100 to 3 concentrations of a drinking water mutagen -chloro-4-(dichloromethyl)-5-hydroxy2(5H)-furanone (MX). The mutagenicity of MX in strain TA100 was evaluated in a 30min suspension assay, and the mutagenic potency was 615 rev/?M (r2 = 1.0). In addition to mutagenicity, gene expression also increased with MX concentration. At 0.46 uM and 1.15 uM, MX increased gene expression of 8 genes by =50%, and at 2.30 uM, MX increased expression of 39 genes by =50%. Among these 39 genes, 15% were involved in energy production and conversion, and 10% were involved in cell motility. Among the 6 genes that were most responsive to MX treatment, all demonstrated a monotonically increasing response to the three concentrations of MX. Three of these genes were associated with the stress response: cpxP specifies a periplasmic protein that combats the lethal phenotype associated with the synthesis of a toxic envelope protein; recA binds to ssDNA and activates DNA repair; and rmf binds 70S ribosomes to form 100S particles that suppress protein synthesis under stress conditions. The other 3 genes (nanH, ftsI, and STM0718) do not have established connections to the stress response. nanH is a neuraminidase; ftsI is required for cell division; and STMO718 is a putative cytoplasmic protein with no known function. These data indicate that MX, in addition to inducing mutations, also induces expression of genes involved in the SOS response as well as other genes. [Abstract does not necessarily reflect the policy of the US EPA.]