Potent intracellular oxidative stress exerted by the carcinogen 4-nitroquinoline-N-oxide

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1993-07, Vol.53 (14), p.3250-3252
Main Authors: NUNOSHIBA, T, DEMPLE, B
Format: Article
Language:English
Subjects:
4-Nitroquinoline-1-oxide - analogs & derivatives
4-Nitroquinoline-1-oxide - pharmacology
Bacterial Proteins - biosynthesis
Bacterial Proteins - genetics
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
Escherichia coli - genetics
Escherichia coli Proteins
Hydrogen Peroxide - metabolism
Medical sciences
Methylphenazonium Methosulfate - pharmacology
Oxidation-Reduction - drug effects
Superoxide Dismutase - pharmacology
Superoxides - metabolism
Trans-Activators
Transcription Factors - biosynthesis
Transcription Factors - genetics
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445