title: DNA interstrand cross-linking by epichlorohydrin.
abstract: Epichlorohydrin (ECH), an important industrial chemical, is a bifunctional alkylating agent with the potential to form DNA cross-links. Occupational exposure to this suspect carcinogen leads to chromosomal aberrations, and ECH has been shown previously to undergo reaction with DNA in vivo and in vitro. We used denaturing polyacrylamide gel electrophoresis to monitor the possible formation of interstrand cross-links within DNA oligomers by ECH and the related compound, epibromohydrin (EBH). Although both compounds did indeed form cross-links between deoxyguanosine residues, EBH was a more efficient cross-linker than ECH. The optimal pH for cross-linking also varied, with ECH more efficient at pH 5.0 and EBH more efficient at pH 7.0. Both agents were relatively flexible in the sequences targeted, with comparable efficiencies for 5'-GGC and 5'GC sites. Furthermore, interstrand cross-linking by the two optical isomers of ECH correlated with their relative cytotoxicities, with R-ECH about twice as potent as S-ECH.
authors: Department of Chemistry, Colby College, Waterville Maine 04901, USA.
authors: Keith P
authors: KP
authors: Romano
authors: Adam G
authors: AG
authors: Newman
authors: Rami W
authors: RW
authors: Zahran
authors: Julie T
authors: JT
authors: Millard
mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental / Q000737:chemistry* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004811:Epichlorohydrin / Q000737:chemistry* / Q000633:toxicity; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000473:pathology; D020128:Inhibitory Concentration 50; D013237:Stereoisomerism
chemical_list: D002274:Carcinogens, Environmental; D003432:Cross-Linking Reagents; D017931:DNA Primers; D004811:Epichlorohydrin; D004247:DNA