RRC ID 59061
Author Muenter MM, Aiken A, Akanji JO, Baig S, Bellou S, Carlson A, Conway C, Cowell CM, DeLateur NA, Hester A, Joshi C, Kramer C, Leifer BS, Nash E, Qi MH, Travers M, Wong KC, Hu M, Gou N, Giese RW, Gu AZ, Beuning PJ.
Title The response of Escherichia coli to the alkylating agents chloroacetaldehyde and styrene oxide.
Journal Mutat Res Genet Toxicol Environ Mutagen
Abstract DNA damage is ubiquitous and can arise from endogenous or exogenous sources. DNA-damaging alkylating agents are present in environmental toxicants as well as in cancer chemotherapy drugs and are a constant threat, which can lead to mutations or cell death. All organisms have multiple DNA repair and DNA damage tolerance pathways to resist the potentially negative effects of exposure to alkylating agents. In bacteria, many of the genes in these pathways are regulated as part of the SOS reponse or the adaptive response. In this work, we probed the cellular responses to the alkylating agents chloroacetaldehyde (CAA), which is a metabolite of 1,2-dichloroethane used to produce polyvinyl chloride, and styrene oxide (SO), a major metabolite of styrene used in the production of polystyrene and other polymers. Vinyl chloride and styrene are produced on an industrial scale of billions of kilograms annually and thus have a high potential for environmental exposure. To identify stress response genes in E. coli that are responsible for tolerance to the reactive metabolites CAA and SO, we used libraries of transcriptional reporters and gene deletion strains. In response to both alkylating agents, genes associated with several different stress pathways were upregulated, including protein, membrane, and oxidative stress, as well as DNA damage. E. coli strains lacking genes involved in base excision repair and nucleotide excision repair were sensitive to SO, whereas strains lacking recA and the SOS gene ybfE were sensitive to both alkylating agents tested. This work indicates the varied systems involved in cellular responses to alkylating agents, and highlights the specific DNA repair genes involved in the responses.
Volume 840
Pages 1-10
Published 2019-4
DOI 10.1016/j.mrgentox.2019.02.001
PII S1383-5718(18)30353-X
PMID 30857727
PMC PMC6525637
MeSH Acetaldehyde / analogs & derivatives* Acetaldehyde / pharmacology Alkylating Agents / pharmacology* DNA Damage / drug effects* DNA, Bacterial / genetics Epoxy Compounds / pharmacology* Escherichia coli / drug effects* Escherichia coli / genetics* Esterases / genetics Rec A Recombinases / genetics SOS Response, Genetics / genetics*
Times Cited 1
Prokaryotes E. coli Keio collection