Romano Keith P, Newman Adam G, Zahran Rami W, Millard Julie T
Department of Chemistry, Colby College, Waterville Maine 04901, USA.
Chem Res Toxicol. 2007 May;20(5):832-8. doi: 10.1021/tx700066h. Epub 2007 Apr 19.
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.
环氧氯丙烷（ECH）是一种重要的工业化学品，是一种双功能烷基化剂，有可能形成DNA交联。职业接触这种可疑致癌物会导致染色体畸变，并且ECH先前已被证明在体内和体外都会与DNA发生反应。我们使用变性聚丙烯酰胺凝胶电泳来监测ECH和相关化合物环氧溴丙烷（EBH）在DNA寡聚体内可能形成的链间交联。虽然这两种化合物确实都在脱氧鸟苷残基之间形成了交联，但EBH是比ECH更有效的交联剂。交联的最佳pH值也有所不同，ECH在pH 5.0时更有效，而EBH在pH 7.0时更有效。两种试剂在靶向序列方面相对灵活，对5'-GGC和5'GC位点的效率相当。此外，ECH的两种旋光异构体的链间交联与其相对细胞毒性相关，R-ECH的效力约为S-ECH的两倍。
