Comparative Human Cell Toxicogenomic Analysis of Monohaloacetic Acid Drinking Water Disinfection Byproducts

The monohaloacetic acids (monoHAAs), iodoacetic, bromoacetic and chloroacetic acids are toxic disinfection byproducts. In vitro toxicological end points were integrated with DNA damage and repair pathway-focused toxicogenomic analyses to evaluate monoHAA-induced alterations of gene expression in nor...

Full description

Saved in:
Bibliographic Details
Published in:Environmental science & technology 2010-10, Vol.44 (19), p.7206-7212
Main Authors: Attene-Ramos, Matias S., Wagner, Elizabeth D., Plewa, Michael J.
Format: Article
Language:English
Subjects:
Acetates - chemistry
Acetates - toxicity
Acids
Apoptosis
Applied sciences
Cell cycle
Cell Line
Cells
Disinfectants - toxicity
DNA damage
DNA repair
DNA, Complementary
Drinking water
Electrophoresis - methods
Exact sciences and technology
Gene expression
Genomics
Halogens - chemistry
Humans
Intestine, Small - drug effects
Pollution
Polymerase Chain Reaction
Toxicity
Toxicology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The monohaloacetic acids (monoHAAs), iodoacetic, bromoacetic and chloroacetic acids are toxic disinfection byproducts. In vitro toxicological end points were integrated with DNA damage and repair pathway-focused toxicogenomic analyses to evaluate monoHAA-induced alterations of gene expression in normal nontransformed human cells. When compared to concurrent control transcriptome profiles, metabolic pathways involved in the cellular responses to toxic agents were identified and provided insight into the biological mechanisms of toxicity. Using the Database for Annotation, Visualization and Integrated Discovery to analyze the gene array data, the majority of the altered transcriptome profiles were associated with genes responding to DNA damage or those regulating cell cycle or apoptosis. The major pathways involved with altered gene expression were ATM, MAPK, p53, BRCA1, BRCA2, and ATR. These latter pathways highlight the involvement of DNA repair, especially the repair of double strand DNA breaks. All of the resolved pathways are involved in human cell stress response to DNA damage and regulate different stages in cell cycle progression or apoptosis.
ISSN:0013-936X
1520-5851
DOI:10.1021/es1000193