4-Nitroquinoline 1-oxide (also known as 4-NQO, 4NQO, 4Nqo, NQO and NQNO) is a quinoline derivative and a tumorigenic compound used in the assessment of the efficacy of diets, drugs, and procedures in the prevention and treatment of cancer in animal models. It induces DNA lesions usually corrected by nucleotide excision repair.
General
4-nitroquinoline 1-oxide (4NQO) is a quinoline, a carcinogenic and mutagenic chemical. Quinolines, like 4NQO, possess a heterocyclic aromatic structure and the same basic chemical formula of C<sub>9</sub>H<sub>7</sub>N. 4NQO may naturally occur in the environment but is typically manufactured for research purposes. 4NQO is known to mimic the biological effects of ultraviolet light on various organisms. Both 4NQO and its reduced metabolite 4-hydroxyaminoquinoline 1-oxide (4HAQO) bind covalently to cellular macromolecules such as nucleic acids and proteins.
4NQO has been shown to trap topoisomerase I cleavage complexes. It may also induce DNA damage through the production of reactive oxygen species thought to arise from enzymatic reduction of its nitro group, although its exact mechanism is unknown. 4NQO’s reactive oxygen species may serve as a byproduct of DNA damage or signaling molecule from damage. In response to damage from 4NQO, cells attempt to repair and initiate a transcriptional response to detoxify the cell from 4NQO and its metabolites.
Technical
DNA damage by 4NQO is a potent model. 4NQO induces DNA lesions usually corrected by nucleotide excision repair. 4NQO’s four electron reduction product, 4-hydroxyaminoquinoline 1-oxide (4HAQO), is believed to be a carcinogenic metabolite of 4NQO. When 4NQO is metabolized to its electrophilic reactant, selyl-4HAQO, it reacts with DNA to form stable quinolone monoadducts considered responsible for its mutagenicity and genotoxicity. Yrr1 shifts cellular response in resistance to 4NQO and rates of respiration.