Flanking Sequences Modulate Diepoxide and Mustard Cross-Linking Efficiencies at the 5'-GNC Site

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• 作者：Gregory A. Sawyer ; Elizabeth D. Frederick ; and Julie T. Millard
• 刊名：Chemical Research in Toxicology
• 出版年：2004
• 出版时间：August 2004
• 年：2004
• 卷：17
• 期：8
• 页码：1057 - 1063
• 全文大小：97K
• 年卷期：v.17,no.8(August 2004)
• ISSN：1520-5010

文摘

Diepoxybutane, diepoxyoctane, and mechlorethamine are cytotoxic agents that induceinterstrand cross-links between the N7 positions of deoxyguanosine residues on opposite strandsof the DNA duplex preferentially at 5'-GNC sequences. We have systematically varied theidentity of either the base 5' to the cross-linked deoxyguanosine residues or the interveningbase pair to determine flanking sequence effects on cross-linking efficiency. We used syntheticDNA oligomers containing four 5'-N₁GN₂C sites that varied either N₁ or N₂. Interstrand cross-links were purified through denaturing polyacrylamide gel electrophoresis and then subjectedto piperidine cleavage. The amount of cleavage at each deoxyguanosine residue, representativeof cross-linking efficiency at that site, was determined by sequencing gel analysis. Our datasuggest that cross-linking efficiency varies with the identity of N₁ similarly (purines >pyrimidines) for diepoxybutane, diepoxyoctane, and mechlorethamine but that the effects ofN₂ differ for the three compounds.