麻省理工學(xué)院和波士頓大學(xué)的研究人員發(fā)現(xiàn),，藥物羥基脲(hydroxyurea)能夠誘導(dǎo)細(xì)菌產(chǎn)生一種對(duì)自身有毒性的分子從而達(dá)到殺死細(xì)菌的目的。
羥基脲能夠抑制DNA合成過程中一種重要的酶,，因此一直以來,，科學(xué)家都用這種藥物研究大腸桿菌，酵母或哺乳動(dòng)物DNA復(fù)制過程被抑制后的影響,。羥基脲還經(jīng)常在化療中用于種植癌細(xì)胞的生長,。
該課題組研究表明，當(dāng)細(xì)胞接受羥基脲治療后,，細(xì)胞不會(huì)因DNA復(fù)制過程被阻斷而發(fā)生立即死亡,，但細(xì)胞內(nèi)會(huì)積累大量的羥基自由基，這些自由基活性水平很高,，并能夠損壞細(xì)胞內(nèi)的核酸,，脂質(zhì)以及蛋白質(zhì)分子。
該課題組研究人員將大腸桿菌用羥基脲進(jìn)行處理,，引起細(xì)菌激活自身的DNA修復(fù)系統(tǒng),，這種應(yīng)答能使細(xì)菌接受藥物處理后還能存活幾個(gè)小時(shí)，但是,，當(dāng)羥基自由基產(chǎn)生后,，全部死亡。（生物谷Bioon.com）
生物谷推薦原始出處：
Molecular Cell,11 December 2009 doi:10.1016/j.molcel.2009.11.024
Hydroxyurea Induces Hydroxyl Radical-Mediated Cell Death in Escherichia coli
Bryan W. Davies1, Michael A. Kohanski3, 4, Lyle A. Simmons1, 6, 7, Jonathan A. Winkler5, 7, James J. Collins2, 4 and Graham C. Walker1, ,
1 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
2 Howard Hughes Medical Institute, Department of Biomedical Engineering, Center for BioDynamics, and Center for Advanced Biotechnology, Boston University, Boston, MA, USA
3 Department of Biomedical Engineering and Center for BioDynamics, Boston University, Boston, MA, USA
4 Boston University School of Medicine, Boston University, Boston, MA, USA
5 Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, Boston, MA, USA
6 Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Hydroxyurea (HU) specifically inhibits class I ribonucleotide reductase (RNR), depleting dNTP pools and leading to replication fork arrest. Although HU inhibition of RNR is well recognized, the mechanism by which it leads to cell death remains unknown. To investigate the mechanism of HU-induced cell death, we used a systems-level approach to determine the genomic and physiological responses of E. coli to HU treatment. Our results suggest a model by which HU treatment rapidly induces a set of protective responses to manage genomic instability. Continued HU stress activates iron uptake and toxins MazF and RelE, whose activity causes the synthesis of incompletely translated proteins and stimulation of envelope stress responses. These effects alter the properties of one of the cell's terminal cytochrome oxidases, causing an increase in superoxide production. The increased superoxide production, together with the increased iron uptake, fuels the formation of hydroxyl radicals that contribute to HU-induced cell death.
