Nunoshiba T, Demple B
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115.
Cancer Res. 1993 Jul 15;53(14):3250-2.
Oxidative stress exerted by superoxide-generating (redox-cycling) agents such as paraquat triggers the soxRS regulon of Escherichia coli. In this system, SoxR protein is the redox-sensitive activator of the soxS gene, the product of which then activates the approximately 10 promoters of this regulon. We found that 4-nitroquinoline-N-oxide (4NQO) is a powerful inducer of soxS, > 10-fold more potent than paraquat. The transcriptional induction of the soxS gene by 4NQO was tightly dependent on a functional soxR gene and on the presence of molecular oxygen, as found previously for several well characterized redox-cycling agents. Two 4NQO-related compounds were also shown to induce soxS:4-nitropyridine-N-oxide, with an efficiency only slightly less than 4NQO, and 4-hydroxyaminoquinoline-N-oxide, at approximately 50-fold lower potency than 4NQO. E. coli strains that are hypersensitive to oxidative stress (owing to deficiency in either superoxide dismutases or oxidative DNA repair enzymes) were hypersensitive to killing by 4NQO. Thus, considerable oxidative stress is induced in cells by 4NQO, which might contribute to the carcinogenic potency of this compound.
由百草枯等超氧化物生成（氧化还原循环）剂施加的氧化应激会触发大肠杆菌的soxRS调节子。在这个系统中，SoxR蛋白是soxS基因的氧化还原敏感激活剂，其产物随后激活该调节子的大约10个启动子。我们发现4-硝基喹啉-N-氧化物（4NQO）是soxS的强力诱导剂，其效力比百草枯高10倍以上。如先前对几种特征明确的氧化还原循环剂所发现的那样，4NQO对soxS基因的转录诱导紧密依赖于功能性soxR基因和分子氧的存在。两种与4NQO相关的化合物也被证明可诱导soxS：4-硝基吡啶-N-氧化物，其效率仅略低于4NQO，以及4-羟基氨基喹啉-N-氧化物，其效力比4NQO低约50倍。对氧化应激敏感的大肠杆菌菌株（由于超氧化物歧化酶或氧化性DNA修复酶缺乏）对4NQO杀伤敏感。因此，4NQO在细胞中诱导了相当大的氧化应激，这可能有助于该化合物的致癌效力。
