Intermolecular linking and fragmentation of DNA by beta-propiolactone, a monoalkylating carcinogen.
Brief exposure to beta-propiolactone (BPL) increases the sedimentation rate of purified Escherichia coli DNA in neutral and alkaline sucrose gradients. However, when electrophoresed in polyacrylamide-agarose gels, this BPL-treated DNA moves ahead of the control. Longer incubation with BPL gives rise to two new fractions, the first one sedimenting as a heterogeneous material of 6-8S, and the second one of very high sedimentation velocity. In acrylamide-agarose gels, the first fraction is again recovered in the 6-8S area, while the second fraction does not enter the gel at all. The DNA at this stage is hyperchromic in ultraviolet light suggesting that as much as 20% may be denaturated. Coliphage lambda DNA treated briefly with BPL and spread in a protein monolayer appears under the electron microscope as a rigid, extended molecule, up to 15% longer than the control DNA, and usually in compact, folded configurations suggesting intramolecular linking. After longer exposure, localized denaturation associated with single-strand breaks is observed. The single-stranded "whiskers" then interact with other DNA molecules, creating highly complex branched networks of single- and multi-stranded DNA. The possible relevance of these observations to the mechanisms involved in carcinogenesis and mutagenesis is considered.
D000477:Alkylating Agents; D002273:Carcinogens; D002499:Centrifugation, Density Gradient; D003090:Coliphages; D004267:DNA Viruses; D004269:DNA, Bacterial / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D004586:Electrophoresis; D004926:Escherichia coli; D007783:Lactones / Q000494:pharmacology*; D008854:Microscopy, Electron; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology
D000477:Alkylating Agents; D002273:Carcinogens; D004269:DNA, Bacterial; D004279:DNA, Viral; D007783:Lactones; D011422:Propionates