麻省理工学院和波士顿大学的研究人员发现，药物羟基脲(hydroxyurea)能够诱导细菌产生一种对自身有毒性的分子从而达到杀死细菌的目的。
羟基脲能够抑制DNA合成过程中一种重要的酶，因此一直以来，科学家都用这种药物研究大肠杆菌，酵母或哺乳动物DNA复制过程被抑制后的影响。羟基脲还经常在化疗中用于种植癌细胞的生长。
该课题组研究表明，当细胞接受羟基脲治疗后，细胞不会因DNA复制过程被阻断而发生立即死亡，但细胞内会积累大量的羟基自由基，这些自由基活性水平很高，并能够损坏细胞内的核酸，脂质以及蛋白质分子。
该课题组研究人员将大肠杆菌用羟基脲进行处理，引起细菌激活自身的DNA修复系统，这种应答能使细菌接受药物处理后还能存活几个小时，但是，当羟基自由基产生后，全部死亡。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
